RESUMEN

Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for potential clinical applications because of their accessibility and anti-inflammatory capacity. We previously demonstrated that DT-MSCs from dental pulp (DP-MSCs), periodontal ligaments (PDL-MSCs), and gingival tissue (G-MSCs) show immunosuppressive effects similar to those of BM, but to date, the DT-MSC-mediated immunoregulation of T lymphocytes through the purinergic pathway remains unknown. In the present study, we compared DP-MSCs, PDL-MSCs, and G-MSCs in terms of CD26, CD39, and CD73 expression; their ability to generate adenosine (ADO) from ATP and AMP; and whether the concentrations of ADO that they generate induce an immunomodulatory effect on T lymphocytes. BM-MSCs were included as the gold standard. Our results show that DT-MSCs present similar characteristics among the different sources analyzed in terms of the properties evaluated; however, interestingly, they express more CD39 than BM-MSCs; therefore, they generate more ADO from ATP. In contrast to those produced by BM-MSCs, the concentrations of ADO produced by DT-MSCs from ATP inhibited the proliferation of CD3+ T cells and promoted the generation of CD4+CD25+FoxP3+CD39+CD73+ Tregs and Th17+CD39+ lymphocytes. Our data suggest that DT-MSCs utilize the adenosinergic pathway as an immunomodulatory mechanism and that this mechanism is more efficient than that of BM-MSCs.

Asunto(s)

5'-Nucleotidasa , Adenosina , Apirasa , Pulpa Dental , Células Madre Mesenquimatosas , Ligamento Periodontal , Linfocitos T , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/inmunología , Humanos , Adenosina/metabolismo , Pulpa Dental/citología , Pulpa Dental/inmunología , Pulpa Dental/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , 5'-Nucleotidasa/metabolismo , Apirasa/metabolismo , Ligamento Periodontal/citología , Ligamento Periodontal/metabolismo , Adenosina Trifosfato/metabolismo , Células Cultivadas , Encía/citología , Encía/metabolismo , Encía/inmunología , Antígenos CD/metabolismo , Inmunomodulación , Diferenciación Celular , Proliferación Celular , Dipeptidil Peptidasa 4/metabolismo , Transducción de Señal , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Proteínas Ligadas a GPI

RESUMEN

Cannabinoids, derived from the Cannabis sativa plant, have garnered increasing attention for their potential therapeutic applications in various diseases. The pharmacologically active compounds in Cannabis, such as delta-9-tetrahydrocannabinol and cannabidiol, exhibit diverse immunomodulatory properties. Although studies have explored the effects of cannabinoids on immune function, their specific interactions with the thymus, a primary immune organ critical for T-cell development and maturation, remain an intriguing area of investigation. As the thymus plays a fundamental role in shaping the immune repertoire, understanding the interplay between cannabinoids and thymic function may shed light on potential benefits or concerns associated with Cannabis-based therapies. This article aims to provide an overview of the current scientific knowledge regarding the impact of medicinal Cannabis on the thymus and its implications for disease treatment and immune health.

Asunto(s)

Cannabinoides , Timo , Timo/efectos de los fármacos , Humanos , Animales , Marihuana Medicinal/uso terapéutico , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología

RESUMEN

BACKGROUND: The LYP tyrosine phosphatase presents a SNP (1858C > T) that increases the risk of developing autoimmune diseases such as type I diabetes and arthritis. It remains unclear how this SNP affects LYP function and promotes the development of these diseases. The scarce information about LYP substrates is in part responsible for the poor understanding of LYP function. RESULTS: In this study, we identify in T lymphocytes several adaptor proteins as potential substrates targeted by LYP, including FYB, SLP-76, HS-1, Vav, SKAP1 and SKAP2. We also show that LYP co-localizes with SLP76 in microclusters, upon TCR engagement. CONCLUSIONS: These data indicate that LYP may modulate T cell activation by dephosphorylating several adaptor proteins, such as FYB, SLP-76, HS-1, Vav, SKAP1 and SKAP2 upon TCR engagement.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales , Fosfoproteínas , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Linfocitos T , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Células Jurkat , Activación de Linfocitos , Fosfoproteínas/metabolismo , Fosforilación , Proteínas Tirosina Fosfatasas/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T/metabolismo , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria/genética , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria/metabolismo

RESUMEN

BACKGROUND: Apoptosis, a form of programmed cell death, is critical for the development and homeostasis of the immune system. Chimeric antigen receptor T (CAR-T) cell therapy, approved for hematologic cancers, retains several limitations and challenges associated with ex vivo manipulation, including CAR T-cell susceptibility to apoptosis. Therefore, strategies to improve T-cell survival and persistence are required. Mesenchymal stem/stromal cells (MSCs) exhibit immunoregulatory and tissue-restoring potential. We have previously shown that the transfer of umbilical cord MSC (UC-MSC)-derived mitochondrial (MitoT) prompts the genetic reprogramming of CD3+ T cells towards a Treg cell lineage. The potency of T cells plays an important role in effective immunotherapy, underscoring the need for improving their metabolic fitness. In the present work, we evaluate the effect of MitoT on apoptotis of native T lymphocytes and engineered CAR-T cells. METHODS: We used a cell-free approach using artificial MitoT (Mitoception) of UC-MSC derived MT to peripheral blood mononuclear cells (PBMCs) followed by RNA-seq analysis of CD3+ MitoTpos and MitoTneg sorted cells. Target cell apoptosis was induced with Staurosporine (STS), and cell viability was evaluated with Annexin V/7AAD and TUNEL assays. Changes in apoptotic regulators were assessed by flow cytometry, western blot, and qRT-PCR. The effect of MitoT on 19BBz CAR T-cell apoptosis in response to electroporation with a non-viral transposon-based vector was assessed with Annexin V/7AAD. RESULTS: Gene expression related to apoptosis, cell death and/or responses to different stimuli was modified in CD3+ T cells after Mitoception. CD3+MitoTpos cells were resistant to STS-induced apoptosis compared to MitoTneg cells, showing a decreased percentage in apoptotic T cells as well as in TUNEL+ cells. Additionally, MitoT prevented the STS-induced collapse of the mitochondrial membrane potential (MMP) levels, decreased caspase-3 cleavage, increased BCL2 transcript levels and BCL-2-related BARD1 expression in FACS-sorted CD3+ T cells. Furthermore, UC-MSC-derived MitoT reduced both early and late apoptosis in CAR-T cells following electroporation, and exhibited an increasing trend in cytotoxic activity levels. CONCLUSIONS: Artificial MitoT prevents STS-induced apoptosis of human CD3+ T cells by interfering with the caspase pathway. Furthermore, we observed that MitoT confers protection to apoptosis induced by electroporation in MitoTpos CAR T-engineered cells, potentially improving their metabolic fitness and resistance to environmental stress. These results widen the physiological perspective of organelle-based therapies in immune conditions while offering potential avenues to enhance CAR-T treatment outcomes where their viability is compromised.

Asunto(s)

Apoptosis , Supervivencia Celular , Células Madre Mesenquimatosas , Mitocondrias , Linfocitos T , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Mitocondrias/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/citología , Receptores Quiméricos de Antígenos/metabolismo , Ingeniería Celular , Cordón Umbilical/citología

RESUMEN

T-cell activation is central for the initiation of T cell mediated adaptive immune response and is the result of the close communication between the Antigen Presenting Cell (APC) and the T lymphocyte. Although T-cell activation is currently well understood, and many intracellular pathways are well characterized, nevertheless new players are constantly identified, and this complements the known protein interactome. In this work we aimed to identify new proteins involved in T cell activation. We reviewed and analyzed results of microarray gene expression datasets reported in the public database GEO-NCBI. Using data from GSE136625, GSE50971, GSE13887, GSE11989 and GSE902 we performed different comparisons using R and other bioinformatic tools including GEO2R and we report here upregulated genes that have no previous reports in immune related functions and with potential participation upon T-cell activation. Our results indicate that RND3, SYT10, IgSF6 and PIN1 are potential new T-cell activation molecules.

Asunto(s)

Biología Computacional , Activación de Linfocitos , Linfocitos T , Activación de Linfocitos/inmunología , Biología Computacional/métodos , Humanos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Perfilación de la Expresión Génica

RESUMEN

Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by the convergence of genetic, immunological, and viral elements resulting in a complex interaction of both internal and external factors. The role of the Epstein-Barr virus (EBV) and human endogenous retroviruses (HERV-E) as triggers and maintenance elements in the pathogenesis of SLE has been widely recognized. Previous studies have independently evaluated the effects of EBV and HERV-E in this disease. In this work, for the first time, these viral factors are jointly investigated in SLE patients. This study aimed at assessing the differential expression of immune regulatory genes and the incidence of specific viral pathogens (EBV and HERV-E), alongside the detailed characterization of surface markers in T- and B-lymphocytes in patients with SLE and control participants. A comparative analysis between patients with SLE and control participants was performed, evaluating the expression of phenotypic markers and genes involved in the immune response (TNF-α, IL-2, IL-6, IL-10, IFNG, TLR3), as well as HERV-E gag and EBV viral genes (LMP1 and BZLF1).A significant association between SLE and EBV was found in this study. A notable increase in EBV LMP1 gene expression was observed in patients with SLE . Also, a significant overexpression of HERV-E was observed, in addition to a considerable increase in the distribution of the cell surface marker CD27 + on T- and B-lymphocytes, observed in individuals with SLE compared to the control group. This study provides evidence regarding the role that EBV virus plays in lymphocytes in the context of SLE, highlighting how both the virus and the host gene expression may influence disease pathogenesis by altering immune regulatory pathways mediated by TNF-α, IFN-γ, and IL-10, as well as parallel overexpression of HERV-E gag. The decrease in TLR3 could indicate a compromised antiviral response, which could facilitate viral reactivation and contribute to disease activity.

Asunto(s)

Retrovirus Endógenos , Herpesvirus Humano 4 , Leucocitos Mononucleares , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/virología , Retrovirus Endógenos/genética , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/genética , Adulto , Femenino , Masculino , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Leucocitos Mononucleares/metabolismo , Perfilación de la Expresión Génica , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/genética , Persona de Mediana Edad , Linfocitos B/inmunología , Linfocitos B/virología , Estudios de Casos y Controles , Linfocitos T/inmunología , Citocinas/metabolismo , Citocinas/genética

RESUMEN

Goto-Kakizaki (GK) rats develop a well-defined insulin resistance (IR) and type 2 diabetes mellitus (T2DM) without presenting obesity. The lymphocyte profile in nonobese diabetic conditions is not yet characterized. Therefore, GK rats were chosen to explore T lymphocyte (TL) dynamics at various stages (21, 60, and 120 days) compared to Wistar rats. GK rats exhibit progressive disruption of glucose regulation, with early glucose intolerance at 21 days and reduced insulin sensitivity at 60 days, confirming IR. Glucose transporter 1 (GLUT1) expression was consistently elevated in GK rats, suggesting heightened TL activation. T-regulatory lymphocyte markers diminished at 21 days. However, GK rats showed increased Th1 markers and reduced Gata-3 expression (crucial for Th2 cell differentiation) at 120 days. These findings underscore an early breakdown of anti-inflammatory mechanisms in GK rats, indicating a proinflammatory TL profile that may worsen chronic inflammation in T2DM.

Asunto(s)

Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Ratas Wistar , Animales , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Ratas , Masculino , Inflamación/metabolismo , Inflamación/patología , Inflamación/inmunología , Factor de Transcripción GATA3/metabolismo , Factor de Transcripción GATA3/genética , Linfocitos T/inmunología , Linfocitos T/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , Células TH1/inmunología , Células TH1/metabolismo

RESUMEN

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy has shown promise in treating hematologic malignancies, yet its potential cardiotoxic effects require thorough investigation. OBJECTIVES: We aim to conduct a systematic review and meta-analysis to examine the cardiotoxic effects of CAR-T therapy in adults with hematologic malignancies. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies reporting cardiovascular outcomes, such as arrhythmias, heart failure, and reduced left ventricle ejection fraction (LVEF). RESULTS: Our analysis of 20 studies involving 4789 patients revealed a 19.68% incidence rate of cardiovascular events, with arrhythmias (7.70%), heart failure (5.73%), and reduced LVEF (3.86%) being the most prevalent. Troponin elevation was observed in 23.61% of patients, while NT-Pro-BNP elevation was observed in 9.4. Subgroup analysis showed higher risks in patients with pre-existing conditions, such as atrial arrhythmia (OR 3.12; p < .001), hypertension (OR 1.85; p = .002), previous heart failure (OR 3.38; p = .003), and coronary artery disease (OR 2.80; p = .003). CONCLUSION: Vigilant cardiovascular monitoring is crucial for patients undergoing CAR-T therapy to enhance safety and treatment efficacy.Novelty Statements.

Asunto(s)

Arritmias Cardíacas , Neoplasias Hematológicas , Cardiotoxicidad , Receptores Quiméricos de Antígenos , Troponina , Linfocitos T , Inmunoterapia Adoptiva , Ventrículos Cardíacos

RESUMEN

Lymphoma is the most common tumor of hematopoietic origin in horses. The course of the disease and clinical signs vary greatly, depending on tumor location and extent. The aim of this report is to describe the occurrence of T-cell-rich oral large B-cell lymphoma with marked local infiltration in a 25-year-old Crioula mare. The mare showed an increase in volume on the right side of its face, dyspnea, anorexia, and progressive weight loss. The clinical assessment showed that the lesion was located in the rostral and caudal sinuses and was markedly invasive to adjacent structures. The autopsy revealed a yellow mass with a soft to firm consistency, infiltrating multiple bones in the skull, and extensively invading the hard palate and masseter muscle. Histologically the mass comprised an undifferentiated malignant neoplasm characterized by a densely cellular neoplasm composed of large CD20 + neoplastic B-lymphocytes admixed with sheets of small, CD3 + reactive T-lymphocytes supported by delicate fibrovascular stroma leading to the diagnosis of oral T-cell-rich large B-cell lymphoma.

Asunto(s)

Enfermedades de los Caballos , Neoplasias de la Boca , Linfocitos T , Animales , Caballos , Femenino , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/diagnóstico , Neoplasias de la Boca/veterinaria , Neoplasias de la Boca/patología , Neoplasias de la Boca/diagnóstico , Linfocitos T/patología , Linfoma de Células B/veterinaria , Linfoma de Células B/patología , Linfoma de Células B/diagnóstico , Resultado Fatal , Linfoma de Células B Grandes Difuso/veterinaria , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/diagnóstico

RESUMEN

CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. However, long-term disease-free survival is still a challenge to overcome. Here, we evaluated the influence of different hinge, transmembrane (TM), and costimulatory CAR domains, as well as manufacturing conditions, cellular product type, doses, patient's age, and tumor types on the clinical outcomes of patients with B cell cancers treated with CD19 CAR T cells. The primary outcome was defined as the best complete response (BCR), and the secondary outcomes were the best objective response (BOR) and 12-month overall survival (OS). The covariates considered were the type of hinge, TM, and costimulatory domains in the CAR, CAR T cell manufacturing conditions, cell population transduced with the CAR, the number of CAR T cell infusions, amount of CAR T cells injected/Kg, CD19 CAR type (name), tumor type, and age. Fifty-six studies (3493 patients) were included in the systematic review and 46 (3421 patients) in the meta-analysis. The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS. The presence of CD28 in the CAR's hinge, TM, and costimulatory domains improved all outcomes evaluated. Doses from one to 4.9 million cells/kg resulted in better clinical outcomes. Our data also suggest that regardless of whether patients have had high objective responses, they might have survival benefits from CD19 CAR T therapy. This meta-analysis is a critical hypothesis-generating instrument, capturing effects in the CD19 CAR T cells literature lacking randomized clinical trials and large observational studies.

Asunto(s)

Antígenos CD19 , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Humanos , Factores de Edad , Antígenos CD19/inmunología , Inmunoterapia Adoptiva/métodos , Leucemia de Células B/terapia , Leucemia de Células B/inmunología , Leucemia de Células B/mortalidad , Linfoma de Células B/inmunología , Linfoma de Células B/terapia , Linfoma de Células B/mortalidad , Receptores de Antígenos de Linfocitos T/inmunología , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunología , Resultado del Tratamiento

RESUMEN

T-cell malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), present significant challenges to treatment due to their aggressive nature and chemoresistance. Chemotherapies remain a mainstay for their management, but the aggressiveness of these cancers and their associated toxicities pose limitations. Immunepotent CRP (ICRP), a bovine dialyzable leukocyte extract, has shown promise in inducing cytotoxicity against various cancer types, including hematological cancers. In this study, we investigated the combined effect of ICRP with a panel of chemotherapies on cell line models of T-ALL and T-LBL (CEM and L5178Y-R cells, respectively) and its impact on immune system cells (peripheral blood mononuclear cells, splenic and bone marrow cells). Our findings demonstrate that combining ICRP with chemotherapies enhances cytotoxicity against tumoral T-cell lymphoblasts. ICRP + Cyclophosphamide (CTX) cytotoxicity is induced through a caspase-, reactive oxygen species (ROS)-, and calcium-dependent mechanism involving the loss of mitochondrial membrane potential, an increase in ROS production, and caspase activation. Low doses of ICRP in combination with CTX spare non-tumoral immune cells, overcome the bone marrow-induced resistance to CTX cell death, and improves the CTX antitumor effect in vivo in syngeneic Balb/c mice challenged with L5178Y-R. This led to a reduction in tumor volume and a decrease in Ki-67 proliferation marker expression and the granulocyte/lymphocyte ratio. These results set the basis for further research into the clinical application of ICRP in combination with chemotherapeutic regimens for improving outcomes in T-cell malignancies.

Asunto(s)

Ciclofosfamida , Especies Reactivas de Oxígeno , Animales , Ratones , Humanos , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Ciclofosfamida/farmacología , Sinergismo Farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Apoptosis/efectos de los fármacos , Bovinos , Muerte Celular/efectos de los fármacos , Antineoplásicos/farmacología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos

RESUMEN

Aim: To investigate the effect of surfactant type on curcumin-loaded (CUR) PLGA nanoparticles (NPs) to modulate monocyte functions. Materials & methods: The nanoprecipitation method was used, and PLGA NPs were designed using Pluronic F127 (F127) and/or lecithin (LEC) as surfactants. Results: The Z-average of the NPs was <200 nm, they had a spherical shape, Derjaguin-Muller-Toporov modulus >0.128 MPa, they were stable during storage at 4°C, ζ-potential ∼-40 mV, polydispersity index <0.26 and % EE of CUR >94%. PLGA-LEC/F127 NPs showed favorable physicochemical and nanomechanical properties. These NPs were bound and internalized mainly by monocytes, suppressed monocyte-induced reactive oxygen species production, and decreased the ability of monocytes to modulate T-cell proliferation. Conclusion: These results demonstrate the potential of these NPs for targeted therapy.

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This study explores how different surfactants affect curcumin-loaded PLGA nanoparticles, a biodegradable polymer. The nanoparticles were designed using Pluronic F127 and/or lecithin as surfactants. They are less than 200 nm and spherical. They are stable when stored at 4 °C, with a surface charge of about -40 mV, and can encapsulate more than 94% of curcumin.The results of this study are promising, showing that PLGA nanoparticles using a mixture of lecithin and Pluronic F127 as surfactants have favorable properties toward monocyte adhesion. They are primarily taken up by monocytes, a type of white blood cell, and demonstrate a remarkable ability to reduce the production of reactive oxygen species, which can cause cell damage, as well as the ability of monocytes to stimulate the proliferation of T cells. This underscores the potential of these nanoparticles in targeted therapy, particularly in diseases where monocytes play a pivotal role, such as chronic inflammatory conditions.

Asunto(s)

Curcumina , Lecitinas , Monocitos , Nanopartículas , Poloxámero , Humanos , Proliferación Celular/efectos de los fármacos , Curcumina/química , Curcumina/farmacología , Portadores de Fármacos/química , Lecitinas/química , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Nanopartículas/química , Tamaño de la Partícula , Poloxámero/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Especies Reactivas de Oxígeno/metabolismo , Tensoactivos/química , Linfocitos T/efectos de los fármacos

RESUMEN

Introduction: Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. Methods: This study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Results: Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells. Discussion: The AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.

Asunto(s)

Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Activación de Linfocitos , Virus de la Enfermedad de Newcastle , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , COVID-19/inmunología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Anticuerpos Antivirales/inmunología , Virus de la Enfermedad de Newcastle/inmunología , Vacunas contra la COVID-19/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Activación de Linfocitos/inmunología , Adulto , Femenino , Masculino , Persona de Mediana Edad , Linfocitos T/inmunología , Vacuna BNT162/inmunología , Vacunación , Vectores Genéticos/genética , Vectores Genéticos/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo

RESUMEN

Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral rotavirus vaccines in young children may be affected by significant immunological differences between individuals in early life and adults. Therefore, understanding the dynamics of early-life systemic and mucosal immune responses and the factors that affect them is essential to improve the current rotavirus vaccines and develop the next generation of mucosal vaccines. This review focuses on the advances in T-cell development during early life in mice and humans, discussing how immune homeostasis and response to pathogens is established in this period compared to adults. Finally, the review explores how this knowledge of early-life T-cell immunity could be utilized to enhance current and novel rotavirus vaccines.

Asunto(s)

Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Linfocitos T , Vacunas contra Rotavirus/inmunología , Vacunas contra Rotavirus/administración & dosificación , Humanos , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/inmunología , Animales , Rotavirus/inmunología , Linfocitos T/inmunología , Administración Oral , Inmunidad Mucosa , Ratones

RESUMEN

BACKGROUND: Previous studies have shown that at least a of intraoral eosinophilic ulcer is best classified as a CD30 + T-cell lymphoproliferative disorder (LPD), with histopathology reminiscent of lymphomatoid papulosis (LyP) of the skin. Microscopically, a mixed population of inflammatory cells, often including eosinophils and varying numbers of atypical lymphoid cells, frequently expressing CD30, is typical for LyP, whose clinicopathological spectrum includes type A, B, C, D, E, and LyP with DUSP22/IRF4 rearrangement. To date, about 27 intraoral LyP cases have been reported. Of them, 7 cases were diagnosed as LyP type C, which is frequently confused with anaplastic large cell lymphoma (ALCL) on histopathology. METHODS: A 60-year-old male was referred for a one-month history of a tongue ulcer. RESULTS: Microscopy showed numerous subepithelial atypical large lymphoid cells, which expressed CD4 (with partial loss of CD3, CD5, and CD7), CD8 (few cells), CD30 (about 50%, in non-diffuse pattern with size variability), TIA-1, and Ki-67 (85%), without staining for CD56, ALK, LMP1, and EBER1/2, concerning for a diagnosis of ALCL. However, after three weeks, the lesion completely healed. CONCLUSION: We present here a rare case of intraoral CD30+ T-cell LPD that we believe is the oral counterpart of cutaneous LyP type C.

Asunto(s)

Antígeno Ki-1 , Papulosis Linfomatoide , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Inmunohistoquímica , Antígeno Ki-1/metabolismo , Papulosis Linfomatoide/patología , Papulosis Linfomatoide/diagnóstico , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/diagnóstico , Linfocitos T/patología

RESUMEN

BACKGROUND: In most cases, Zika virus (ZIKV) causes a self-limited acute illness in adults, characterized by mild clinical symptoms that resolve within a few days. Immune responses, both innate and adaptive, play a central role in controlling and eliminating virus-infected cells during the early stages of infection. AIM: To test the hypothesis that circulating T cells exhibit phenotypic and functional activation characteristics during the viremic phase of ZIKV infection. METHODS: A comprehensive analysis using mass cytometry was performed on peripheral blood mononuclear cells obtained from patients with acute ZIKV infection (as confirmed by RT-PCR) and compared with that from healthy donors (HD). The frequency of IFN-γ-producing T cells in response to peptide pools covering immunogenic regions of structural and nonstructural ZIKV proteins was quantified using an ELISpot assay. RESULTS: Circulating CD4+ and CD8+ T lymphocytes from ZIKV-infected patients expressed higher levels of IFN-γ and pSTAT-5, as well as cell surface markers associated with proliferation (Ki-67), activation ((HLA-DR, CD38) or exhaustion (PD1 and CTLA-4), compared to those from HD. Activation of CD4+ and CD8+ memory T cell subsets, including Transitional Memory T Cells (TTM), Effector Memory T cells (TEM), and Effector Memory T cells Re-expressing CD45RA (TEMRA), was prominent among CD4+ T cell subset of ZIKV-infected patients and was associated with increased levels of IFN-γ, pSTAT-5, Ki-67, CTLA-4, and PD1, as compared to HD. Additionally, approximately 30% of ZIKV-infected patients exhibited a T cell response primarily directed against the ZIKV NS5 protein. CONCLUSION: Circulating T lymphocytes spontaneously produce IFN-γ and express elevated levels of pSTAT-5 during the early phase of ZIKV infection whereas recognition of ZIKV antigen results in the generation of virus-specific IFN-γ-producing T cells.

Asunto(s)

Linfocitos T CD8-positivos , Interferón gamma , Infección por el Virus Zika , Virus Zika , Humanos , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/epidemiología , Adulto , Virus Zika/inmunología , Femenino , Masculino , Interferón gamma/metabolismo , Interferón gamma/inmunología , Brasil/epidemiología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , Persona de Mediana Edad , Adulto Joven , Epidemias , Activación de Linfocitos/inmunología , Linfocitos T/inmunología

RESUMEN

Toxoplasmosis is the most prevalent parasitic zoonosis worldwide, causing ocular and neurological diseases. No vaccine has been approved for human use. We evaluated the response of peripheral blood mononuclear cells (PBMCs) to a novel construct of Toxoplasma gondii total antigen in maltodextrin nanoparticles (NP/TE) in individuals with varying infectious statuses (uninfected, chronic asymptomatic, or ocular toxoplasmosis). We analyzed the concentration of IFN-γ after NP/TE ex vivo stimulation using ELISA and the immunophenotypes of CD4+ and CD8+ cell populations using flow cytometry. In addition, serotyping of individuals with toxoplasmosis was performed by ELISA using GRA6-derived polypeptides. Low doses of NP/TE stimulation (0.9 µg NP/0.3 µg TE) achieved IFN-γ-specific production in previously exposed human PBMCs without significant differences in the infecting serotype. Increased IFN-γ expression in CD4+ effector memory cell subsets was found in patients with ocular toxoplasmosis with NP/TE but not with TE alone. This is the first study to show how T-cell subsets respond to ex vivo stimulation with a vaccine candidate for human toxoplasmosis, providing crucial insights for future clinical trials.

Asunto(s)

Antígenos de Protozoos , Interferón gamma , Activación de Linfocitos , Nanopartículas , Polisacáridos , Toxoplasma , Toxoplasmosis , Humanos , Nanopartículas/química , Polisacáridos/inmunología , Toxoplasma/inmunología , Antígenos de Protozoos/inmunología , Toxoplasmosis/inmunología , Interferón gamma/metabolismo , Interferón gamma/inmunología , Activación de Linfocitos/inmunología , Femenino , Adulto , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Masculino , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Persona de Mediana Edad

RESUMEN

Sympathetic ophthalmia is a rare and potentially devastating bilateral diffuse granulomatous panuveitis. It is caused by surgical or non-surgical eye injuries and is an uncommon and serious complication of trauma. It is diagnosed clinically and supported by imaging examinations such as ocular ultrasonography and optical coherence tomography. Its treatment consists of immunosuppressive therapy with steroids and sometimes steroid-sparing drugs, such as cyclosporine, azathioprine, cyclophosphamide, and mycophenolate mofetil. Fast and effective management with systemic immunosuppressive agents allows for disease control and achievement of good visual acuity in the sympathizing eye. By contrast, enucleation should be considered only in situations where the injured eye has no light perception or in the presence of severe trauma. In addition to a bibliographic review of this topic, we report six cases involving different immunosuppressive and surgical treatment modalities.

Asunto(s)

Inmunosupresores , Oftalmía Simpática , Humanos , Oftalmía Simpática/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Linfocitos T/inmunología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual

RESUMEN

Parasites possess remarkable abilities to evade and manipulate the immune response of their hosts. Echinococcus granulosus is a parasitic tapeworm that causes cystic echinococcosis in animals and humans. The hydatid fluid released by the parasite is known to contain various immunomodulatory components that manipulate host´s defense mechanism. In this study, we focused on understanding the effect of hydatid fluid on dendritic cells and its impact on autophagy induction and subsequent T cell responses. Initially, we observed a marked downregulation of two C-type lectin receptors in the cell membrane, CLEC9A and CD205 and an increase in lysosomal activity, suggesting an active cellular response to hydatid fluid. Subsequently, we visualized ultrastructural changes in stimulated dendritic cells, revealing the presence of macroautophagy, characterized by the formation of autophagosomes, phagophores, and phagolysosomes in the cell cytoplasm. To further elucidate the underlying molecular mechanisms involved in hydatid fluid-induced autophagy, we analyzed the expression of autophagy-related genes in stimulated dendritic cells. Our results demonstrated a significant upregulation of beclin-1, atg16l1 and atg12, indicating the induction of autophagy machinery in response to hydatid fluid exposure. Additionally, using confocal microscopy, we observed an accumulation of LC3 in dendritic cell autophagosomes, confirming the activation of this catabolic pathway associated with antigen presentation. Finally, to evaluate the functional consequences of hydatid fluid-induced autophagy in DCs, we evaluated cytokine transcription in the splenocytes. Remarkably, a robust polyfunctional T cell response, with inhibition of Th2 profile, is characterized by an increase in the expression of il-6, il-10, il-12, tnf-α, ifn-γ and tgf-ß genes. These findings suggest that hydatid fluid-induced autophagy in dendritic cells plays a crucial role in shaping the subsequent T cell responses, which is important for a better understanding of host-parasite interactions in cystic echinococcosis.

Asunto(s)

Autofagia , Células Dendríticas , Equinococosis , Echinococcus granulosus , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Animales , Echinococcus granulosus/inmunología , Autofagia/inmunología , Equinococosis/inmunología , Equinococosis/parasitología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Ratones , Lectinas Tipo C/metabolismo , Citocinas/metabolismo , Femenino , Autofagosomas/inmunología , Autofagosomas/metabolismo

RESUMEN

Interleukin (IL)-33 is an important cytokine in the tumour microenvironment; it is known to promote the growth and metastasis of solid cancers, such as gastric, colorectal, ovarian and breast cancer. Our group demonstrated that the IL-33/ST2 pathway enhances the development of squamous cell carcinoma (SCC). Conversely, other researchers have reported that IL-33 inhibits tumour progression. In addition, the crosstalk between IL-33, cancer cells and immune cells in SCC remains unknown. The aim of this study was to investigate the effect of IL-33 on the biology of head and neck SCC lines and to evaluate the impact of IL-33 neutralisation on the T cell response in a preclinical model of SCC. First, we identified epithelial and peritumoural cells as a major local source of IL-33 in human SCC samples. Next, in vitro experiments demonstrated that the addition of IL-33 significantly increased the proliferative index, motility and invasiveness of SCC-25 cells, and downregulated MYC gene expression in SCC cell lines. Finally, IL-33 blockade significantly delayed SCC growth and led to a marked decrease in the severity of skin lesions. Importantly, anti-IL-33 monoclonal antibody therapy increase the percentage of CD4+IFNγ+ T cells and decreased CD4+ and CD8+ T cells secreting IL-4 in tumour-draining lymph nodes. Together, these data suggest that the IL-33/ST2 pathway may be involved in the crosstalk between the tumour and immune cells by modulating the phenotype of head and neck SCC and T cell activity. IL-33 neutralisation may offer a novel therapeutic strategy for SCC.

Asunto(s)

Carcinoma de Células Escamosas , Movimiento Celular , Proliferación Celular , Interleucina-33 , Activación de Linfocitos , Interleucina-33/metabolismo , Humanos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/metabolismo , Animales , Activación de Linfocitos/inmunología , Invasividad Neoplásica , Ratones , Línea Celular Tumoral , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Microambiente Tumoral/inmunología , Femenino