RESUMEN
Produtos liberados pela queima do cigarro convencional (CC) estão relacionados com a progressão clínica da artrite reumatoide (AR). Produtos fumígenos não combustíveis surgiram com a premissa de apresentarem menor toxicidade que o CC, dentre os quais está o tabaco aquecido (heat-not-burn tobacco; HNBT). Neste projeto investigamos os efeitos do HNBT sobre eventos envolvidos na AR, focando na sintomatologia, expressão de metalotioneínas (MTs), e na biologia de linfócitos T CD4+ primários e da linhagem Jurkat. Exposições in vivo ao ar, CC ou HNBT foram realizadas 2 vezes ao dia, 1 hora cada (12 CC ou 24 HNBT/hora), nos dias 14-21 da indução da artrite induzida por antígeno (AIA) em camundongos C57Bl/6. Foram realizadas análises dos parâmetros clínico da doenças, histopatologia e imunohistoquímica; quantificação de nicotina e cotinina séricas por cromatografia líquida acoplada a espectrometria de massas (MS). Os efeitos das exposições in vitro sobre linfócitos T foram mensurados por citometria de fluxo e ELISA. A concentração de metais emitidas pelo CC ou HNBT durante as exposições foram mensurados por MS com plasma acoplado. Camundongos expostos ao CC apresentaram intensa inflamação pulmonar, expressões acentuadas de MTs hepáticas e pulmonares e exacerbação dos parâmetros de AIA quando comparados ao grupo expostos ao HNBT. Animais expostos ao CC ou ao HNBT apresentaram redução na celularidade de órgãos linfoides. Somente a exposição in vitro ao CC causou estresse oxidativo e secreção de citocinas inflamatórias, ativação do receptor de hidrocarbonetos arila (AhR) e polarização de células Th17. Diferentemente, exposição ao CC ou ao HNBT provocaram redução da secreção de IL-2 e proliferação de células Jurkat. A exposição de células Jurkat à nicotina mimetizou os efeitos inibitórios da exposição ao HNBT sobre a secreção de IL-2 e proliferação de linfócitos T. O CC liberou maiores concentrações de metais nas câmaras de exposição. Associados, nossos resultados mostram que embora exposições ao HNBT não exacerbem parâmetros inflamatórios de AIA e nem em funções linfócitos T, ambos produtos prejudicam a celularidade de órgãos linfoides e a proliferação e secreção de IL-2 por linfócitos T
Products released by burning conventional cigarettes (CC) are related to the worsening of rheumatoid arthritis (RA). Non-combustible smoking products appeared with the premise of presenting less toxicity than the CC, among which is the heated tobacco (heat-not-burn tobacco; HNBT). Here, we investigate the effects of HNBT on events involved in RA, focusing on symptoms, expression of metallothioneins (MTs), and on the biology of primary CD4+ T lymphocytes and the Jurkat T cell lineage. In vivo exposures to air, CC or HNBT were performed twice a day, 1 hour each (12 CC or 24 HNBT / hour), on days 14-21 of the induction of antigen-induced arthritis (AIA) in C57Bl / 6 mice. Analyzes of the clinical parameters of the AIA, histopathology, and immunohistochemistry were performed; quantification of nicotine and cotinine by liquid chromatography coupled to mass spectrometry (MS). The in vitro effects of exposures on T lymphocytes were measured by flow cytometry and ELISA. The concentration of metals released by the CC or HNBT during the exposures was measured by MS with coupled plasma. Mice exposed to CC showed intense pulmonary inflammation, marked expressions of hepatic and pulmonary MTs, and exacerbation of AIA parameters when compared to the group exposed to HNBT. Animals exposed to CC or HNBT showed a reduction in the cellularity of lymphoid organs. Only in vitro exposure to CC caused oxidative stress and secretion of inflammatory cytokines, activation of the aryl hydrocarbon receptor (AhR), and polarization of Th17 cells. However, exposure to CC or HNBT led to reduced secretion of IL-2 and proliferation of Jurkat cells. The exposure of Jurkat T cells to nicotine mimicked the inhibitory effects of exposure to HNBT on IL-2 secretion and T lymphocyte proliferation. The CC released higher concentrations of metals in the exposure chambers. In association, our results show that although exposures to HNBT do not exacerbate inflammatory parameters of AIA or T lymphocyte functions, both products impair lymphoid organ cell function and the proliferation and secretion of IL-2 by T lymphocytes
Asunto(s)
Animales , Masculino , Ratones , Artritis Reumatoide/patología , Humo/efectos adversos , Linfocitos T/clasificación , Metalotioneína/agonistas , Nicotina/efectos adversos , Asociación , Cromatografía Liquida/métodos , Citometría de Flujo/métodosRESUMEN
BACKGROUND: More than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019. OBJECTIVE: We sought to identify and characterize subsets of patients with asthma at increased risk for severe acute respiratory syndrome coronavirus 2 infection. METHODS: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to angiotensin-converting enzyme-2 (ACE2) expression within bronchial epithelium. ACE-2-correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. RESULTS: Stratifying by type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the severe acute respiratory syndrome coronavirus 2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with type 1 and 2 IFN signatures, normally induced by viral infections. T-cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe coronavirus disease 2019, including male sex, history of hypertension, low peripheral blood, and elevated bronchoalveolar lavage lymphocytes. CONCLUSIONS: ACE2 expression is linked to upregulation of viral response genes in a subset of type 2-low patients with asthma with characteristics resembling known risk factors for severe coronavirus disease 2019. Therapies targeting the IFN family and T-cell-activating factors may therefore be of benefit in a subset of patients.
Asunto(s)
Asma/epidemiología , Asma/genética , Infecciones por Coronavirus/epidemiología , Pandemias , Peptidil-Dipeptidasa A/genética , Neumonía Viral/epidemiología , Receptores Virales/genética , Adolescente , Adulto , Enzima Convertidora de Angiotensina 2 , Asma/clasificación , Asma/inmunología , Betacoronavirus/genética , Betacoronavirus/inmunología , Biomarcadores/metabolismo , Bronquios/inmunología , Bronquios/patología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/virología , Eosinófilos/inmunología , Eosinófilos/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Interferón Tipo I/genética , Interferón Tipo I/inmunología , Interferón gamma/genética , Interferón gamma/inmunología , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/inmunología , Neumonía Viral/virología , Mapeo de Interacción de Proteínas , Receptores Virales/inmunología , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Linfocitos T/clasificación , Linfocitos T/inmunología , Linfocitos T/patología , Transcriptoma , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) has been associated with premature immunosenescence and an increased prevalence of age-related morbidities including poor cognitive function. OBJECTIVE: We explored the relationships among lymphocyte subsets and memory in RA. METHODS: Thirty patients with RA and 19 age-matched healthy controls took part in this study. Cognitive function stress and depression scores were evaluated by structured clinical questionnaires. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate the following subsets: B cells, activated and naïve/memory T cells, regulatory FoxP3+ T (Treg) cells, Th17+ cells, NK cells and senescence-associated CD28- T cells. RESULTS: RA patients were more depressed than controls, but stress levels were similar in the 2 groups. Patients had impaired memory performance compared to controls, demonstrated by lower Mini-Mental State Examination scores and logical and working memories (all p < 0.0001). These group effects remained significant after correcting for depression and age. Patients had expansion of regulatory T cells, naïve CD4+ T cells and CD8+CD28- cells but reduced percentages of B cells and memory CD8+CD45RO+ T cells compared to controls. CD8+CD28- and CD8+CD45RO+ T cells were found to be negatively associated with memory. CONCLUSION: RA patients had reduced memory performance compared to healthy controls. Expansion of activated and senescence-associated T cells was correlated with poor memory performance.
Asunto(s)
Artritis Reumatoide/complicaciones , Artritis Reumatoide/patología , Trastornos de la Memoria/etiología , Linfocitos T/patología , Artritis Reumatoide/inmunología , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Estudios de Casos y Controles , Estudios Transversales , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Activación de Linfocitos , Recuento de Linfocitos , Masculino , Escala del Estado Mental , Pruebas Neuropsicológicas , Estrés Psicológico/etiología , Linfocitos T/clasificación , Linfocitos T/inmunología , Linfocitos T Reguladores , Aprendizaje VerbalRESUMEN
OBJECTIVE: The overall objective of this study was to assess the oral manifestations and their association with immunologic status and health history, of individuals with hypogammaglobulinemia. STUDY DESIGN: A case-controlled study of 100 subjects with hypogammaglobulinemia and 93 control individuals was performed. All participants were examined for dental caries, periodontal disease, mucosal lesions/infections, and general oral health problems. Decayed, missing, filled teeth and community periodontal index were recorded. Complete blood count, serum immunoglobulins, and lymphocyte immunophenotyping were measured on the same day of the oral health assessment. RESULTS: Individuals with hypogammaglobulinemia showed higher prevalence of enamel hypoplasia and complaints of dry mouth, and lower prevalence of dental caries and periodontal disease. CONCLUSIONS: The systemic conditions associated with hypogammaglobulinemia were not associated with enhanced susceptibility to caries, gingivitis, or periodontitis; however, individuals with hypogammaglobulinemia were more likely to report more episodes of recurrent aphthous ulcers compared with control individuals.
Asunto(s)
Agammaglobulinemia/complicaciones , Enfermedades de la Boca/etiología , Adolescente , Adulto , Anciano , Linfocitos B/patología , Recuento de Células Sanguíneas , Complejo CD3/análisis , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Estudios de Casos y Controles , Índice CPO , Caries Dental/etiología , Hipoplasia del Esmalte Dental/etiología , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Células Asesinas Naturales/patología , Masculino , Persona de Mediana Edad , Enfermedades Periodontales/etiología , Índice Periodontal , Estomatitis Aftosa/etiología , Estomatitis Herpética/etiología , Linfocitos T/clasificación , Xerostomía/etiología , Adulto JovenRESUMEN
Schizophrenia is characterized by a slow deteriorating mental illness. Although the pathophysiology mechanisms are not fully understood, different studies have suggested a role for the immune system in the pathogenesis of schizophrenia. To date, an altered expression or signaling of neurotransmitters receptors is observed in immune cells during psychiatric disorders. In the present study, we investigated the expression of different serotonin and dopamine receptors in T-cells of schizophrenic and control patients. We used flow cytometry to determine the pattern of expression of dopamine (D2 and D4) and serotonine receptors (SR1A, SR1C, SR2A, SR2B), as well as serotonin transporter (ST), in T-cell subsets (CD4 and CD8). Expression of serotonin receptors and ST in T-cells of schizophrenic patients were not different from controls. However, the percentages of CD4+D4+ and CD8+D4+ were increased in schizophrenic patients as compared to controls. In addition, increased percentages of CD8+D2+ cells were also observed in schizophrenic patients, albeit this population revealed lower CD4+D2+ cells in comparison to controls. Interestingly, a relationship between clinical symptoms and immunological parameters was also observed. We showed that the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were positively related to CD8+D2+ cells, though AIMS was inversely related to CD4+D4+ cells. In conclusion, the alteration in the pattern of cell population and molecules expressed by them might serve as a promising biomarker for diagnosis of schizophrenia.
Asunto(s)
Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D4/metabolismo , Receptores de Serotonina/metabolismo , Esquizofrenia/patología , Linfocitos T/metabolismo , Adulto , Análisis de Varianza , Antígenos CD/metabolismo , Estudios de Casos y Controles , Evaluación de la Discapacidad , Citometría de Flujo , Regulación de la Expresión Génica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Subgrupos de Linfocitos T/metabolismo , Linfocitos T/clasificaciónRESUMEN
The effect of experimental haemonchosis on the number of tissue eosinophils, plasma cells and lymphocyte subpopulations was evaluated in the fundic abomasal region, the pyloric abomasal region and the abomasal lymph node of Blackbelly lambs, which are resistant to infection, and Columbia lambs, which are susceptible to infection. An increase in the number of tissue eosinophils and CD4+ and WC1(+)γδ T-cells was observed in the pyloric abomasal region of Blackbelly lambs and correlated with lower worm burden and greater resistance to infection. Increases in IgA+ plasma cells from the pyloric abomasal region were observed in both infected groups, but there was no difference between the groups. Therefore, increases in IgA+ plasma cells did not explain the resistance observed. Infection caused a significant increase in tissue eosinophils in the abomasal lymph node of Blackbelly lambs and a decrease in the number of CD4+ T-cells in lambs of both breeds. CD8+ T-cells and IgG+ and IgM+ plasma cells were not associated with either infection or resistance. In this work, clear differences were observed in the numbers of CD4+ and WC1(+)γδ T-cells, tissue eosinophils and IgA+ plasma cells between the abomasal regions studied. These differences indicate that the immunological response is not homogenous in all abomasal mucosa and that evaluating the response from a single abomasal region may not be representative of the cellular response across the abomasum.
Asunto(s)
Abomaso/inmunología , Hemoncosis/veterinaria , Haemonchus/clasificación , Enfermedades de las Ovejas/parasitología , Abomaso/citología , Animales , Anticuerpos Antihelmínticos/metabolismo , Heces/parasitología , Predisposición Genética a la Enfermedad , Hemoncosis/inmunología , Haemonchus/inmunología , Inmunoglobulina A/metabolismo , Masculino , Recuento de Huevos de Parásitos , Ovinos , Enfermedades de las Ovejas/genética , Enfermedades de las Ovejas/inmunología , Linfocitos T/clasificación , Linfocitos T/fisiología , Factores de TiempoRESUMEN
HIV coinfection modifies the clinical course of leishmaniasis by promoting a Th2 pattern of cytokine production. However, little information is available regarding the lymphocytic response in untreated coinfected patients. This work presents the immunophenotyping of Leishmania-stimulated T cells from a treatment-naÏve HIV+ patient with ML. Leishmania braziliensis antigens induced CD69 expression on CD3+CD4+ and CD3+CD8+ cells. It also increased IL-4 intracellular staining on CD3+CD4+GATA3- population and decreased the percentage of CD3+CD4+IL-17+ cells. This suggests that modulations in the IL-4R/STAT6 pathway and the Th17 population may serve as parasitic evasion mechanisms in HIV/ML. Further studies are required to confirm these results.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Inmunofenotipificación , Leishmania braziliensis/inmunología , Leishmaniasis Mucocutánea/inmunología , Linfocitos T/inmunología , Adulto , Humanos , Masculino , Linfocitos T/clasificaciónRESUMEN
HIV coinfection modifies the clinical course of leishmaniasis by promoting a Th2 pattern of cytokine production. However, little information is available regarding the lymphocytic response in untreated coinfected patients. This work presents the immunophenotyping of Leishmania-stimulated T cells from a treatment-naÏve HIV+ patient with ML. Leishmania braziliensis antigens induced CD69 expression on CD3+CD4+ and CD3+CD8+ cells. It also increased IL-4 intracellular staining on CD3+CD4+GATA3- population and decreased the percentage of CD3+CD4+IL-17+ cells. This suggests that modulations in the IL-4R/STAT6 pathway and the Th17 population may serve as parasitic evasion mechanisms in HIV/ML. Further studies are required to confirm these results.
A co-infecção por HIV modifica o curso clínico da leishmaniose ao promover aumento no perfil Th2 de produção de citocinas. No entanto, há pouca informação a respeito da resposta linfocitária em pacientes co-infectados sem tratamento. Neste trabalho, foi realizada a imunofenotipagem de células T estimuladas com antígenos de Leishmania braziliensis em paciente não tratado HIV+ e com leishmaniose mucosa. Os resultados mostraram aumento na expressão de CD69 em células CD3+CD4+ e CD3+CD8+. Além disso, foi observado aumento de IL-4 na população de linfócitos CD3+CD4+GATA3- e diminuição no percentual de células CD3+CD4+IL-17+. Estes resultados sugerem que a modulação da via IL-4R/STAT6 e da população de células Th17 funcione como mecanismo de evasão parasitária em HIV/LM. Estudos futuros são necessários para confirmar estes resultados.
Asunto(s)
Adulto , Humanos , Masculino , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Inmunofenotipificación , Leishmania braziliensis/inmunología , Leishmaniasis Mucocutánea/inmunología , Linfocitos T/inmunología , Linfocitos T/clasificaciónRESUMEN
BACKGROUND. We tested the hypothesis that patients who have recovered from leptospirosis have peripheral blood memory T cells that are specific for Leptospira or Leptospira protein antigens. METHODS. Peripheral blood mononuclear cells (PBMCs) were obtained from patients who had recovered from leptospirosis, as well as from control individuals. PBMCs were assessed for in vitro proliferation, phenotyping, and cytokine production after stimulation with different strains of Leptospira, recombinant LipL32, or overlapping synthetic peptides of different outer membrane proteins. RESULTS. PBMCs from both control subjects and patients produced significant proliferative responses to all Leptospira strains. Proliferation from control PBMCs was significantly greater than responses produced by patient PBMCs. Select strains of Leptospira expanded both T cell receptor (TCR) alphabeta and TCRgammadelta T cells in both control subject and patient PBMCs. Patient and control subject PBMCs produced equivalent levels of tumor necrosis factor alpha and interferon gamma, but patient PBMCs produced significantly less interleukin 10 than did control subject PBMCs after stimulation by different strains of Leptospira. PBMCs from patients failed to respond to recombinant LipL32 or to any of the Leptospira peptides. CONCLUSION. Leptospira induced significant proliferative responses, TCRgammadelta T cell expansion, and cytokine production in both control subject and patient PBMCs. Patient PBMCs failed to recognize Leptospira protein antigens. Leptospirosis does not seem to generate memory T cells that can be activated by in vitro stimulation.
Asunto(s)
Memoria Inmunológica , Leptospirosis/inmunología , Linfocitos T/clasificación , Linfocitos T/inmunología , Citocinas/genética , Citocinas/metabolismo , Perfilación de la Expresión Génica , Humanos , Leptospira/clasificación , Leptospira/inmunología , Leptospirosis/epidemiología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/fisiología , Perú/epidemiologíaRESUMEN
Although most T lymphocytes express the alphabeta T-cell receptor and either CD4 or CD8 molecules, a small population of cells lacking these coreceptors, CD4- CD8- (double negative [DN]) T cells, has been identified in the peripheral immune system of mice and humans. To better understand the role that this population may have in the human immune response against Leishmania spp., a detailed study defining the activation state, cytokine profile, and the heterogeneity of DN T cells bearing alphabeta or gammadelta T-cell receptors was performed with a group of well-defined cutaneous leishmaniasis patients. Strikingly, on average 75% of DN T cells from cutaneous leishmaniasis patients expressed the alphabeta T-cell receptor, with the remainder expressing the gammadelta receptor, while healthy donors displayed the opposite distribution with approximately 75% of the DN T cells expressing the gammadelta T-cell receptor. Additionally, alphabeta DN T cells from cutaneous leishmaniasis patients are compatible with previous antigen exposure and recent activation. Moreover, while alphabeta DN T cells from Leishmania-infected individuals present a proinflammatory cytokine profile, gammadelta DN T cells express a regulatory profile exemplified by interleukin-10 production. The balance between these subpopulations could allow for the formation of an effective cellular response while limiting its pathogenic potential.
Asunto(s)
Antígenos CD4 , Antígenos CD8 , Leishmaniasis Cutánea/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Subgrupos de Linfocitos T/inmunología , Linfocitos T/clasificación , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Células Cultivadas , Niño , Preescolar , Citocinas/biosíntesis , Femenino , Humanos , Leishmaniasis Cutánea/metabolismo , Leishmaniasis Cutánea/patología , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/metabolismo , Linfocitos T/metabolismoRESUMEN
There are differences between children and adults in certain aspects of the Helicobacter pylori (HP) infection, among them the lower titre of IgG antibodies anti-HP in the former group. Thus, we investigated by means of flow cytometry CD4+/CD3+ (CD4+T), CD8+/CD3+ (CD8+T) and CD19+/CD3- (B) cells, activation/co-stimulatory markers (CD4+/HLA-DR+, CD4+/CD28+, CD8+/HLA-DR+ and CD8+/CD28+) and by means of ELISA IgG anti-HP antibodies in the peripheral blood from HP-positive and -negative children and adults. An increased CD4+/CD28+ and CD8+/CD28+ percentage and number of CD4+/CD3+ cells were seen in infected adults. Conversely, no difference was observed between infected and noninfected children, but when they were stratified by age, an increased CD4+/CD28+ cell percentage was seen in the HP-positive group older than 10 years. The mean level of IgG anti-HP was lower in younger infected children, increased with age and correlated with CD4+ cells. Our data suggest that the immune response to HP infection vary according to the age. Low percentage of activated CD4+ cell may contribute to the lower level of serum IgG anti-HP observed in younger infected children. In addition, the CD4+ cell participation during the infection seems to begin after 10 years old, when the immune response becomes similar to that seen in adults.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Linfocitos B/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori , Subgrupos Linfocitarios/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Factores de Edad , Anciano , Antígenos CD/análisis , Linfocitos B/clasificación , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Linfocitos T/clasificaciónRESUMEN
HA(306-318) is an immunodominant peptide of the hemagglutinin of influenza virus that binds to most human leukocyte antigen (HLA-DR) alleles, while p18(73-85) is a HIV peptide characterized as a DR101 binding peptide. Our results demonstrate that crystal relaxation leads to the loss of a hydrogen bond between the beta81 histidine and the HA(306-318) peptide. This histidine is also involved in the binding of superantigens like SEA via a coordination of a zinc atom. To monitor the interaction of these peptides with this histidine of HLA-DR molecules, chemical modification, peptide binding on HLA-DR101 wild type and mutated molecules, and proliferation experiments were conducted, together with molecular simulation of HLA-DR/peptide molecular complexes. Our data suggest a different binding peptide pattern, depending of whether the peptide is HLA-DR101 allele specific or a shared one. Furthermore, tyrosine substitution at position beta81 does not affect either peptide binding or HA(306-318) clone-specific T-cell proliferation. On the contrary, the alanine substitution at position HLA-DR101 beta81 abrogated both peptide binding and T-cell proliferation. These results suggest that the histidine 81 on the DRbeta chain plays an important role in the HLA-DR peptide binding, more likely by polar interactions of the amino acid side chain ring with the peptide.
Asunto(s)
Presentación de Antígeno , Antígenos HLA-DR/química , Antígenos HLA-DR/metabolismo , Histidina/metabolismo , Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Animales , Sitios de Unión , Células Cultivadas , Antígenos HLA-DR/genética , Histidina/genética , Humanos , Activación de Linfocitos , Ratones , Modelos Moleculares , Péptidos/metabolismo , Unión Proteica , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T/clasificación , Linfocitos T/metabolismoRESUMEN
The events of the cellular immune response in neurocysticercosis (NC) are not fully understood. Studies of the CD3, CD3/CD4, CD3/CD8, CD45/CD19, and CD45/CD56 molecules and activation-related CD69 molecule in cells from the cerebrospinal fluid (CSF) and peripheral blood (PB) of patients with NC may provide a better elucidation of the inflammatory and immunological events occurring in this disease. Seven patients with NC and 3 individuals with other disorders were evaluated by a three-color flow cytometric method. CD69 was detected in a higher percentage of cells in all CSF samples from patients, but not in PB or CSF from the control group. The percentage of CD3+ cells did not differ significantly in CSF and PB cells from patients and controls. The predominance of CD3+CD8+ cells was observed in CSF from one patient and in PB from 2 patients, who were in stage III of the disease (inflammatory process). The percentage of CD45+CD19+ cells was higher in CSF than in PB from patients who presented anti-cysticercus antibodies in CSF. The percentage of CD45+CD56+ cells in CSF was higher than in PB, but this rate was similar to reference values reported by other authors. Our data suggest that the cytometric method applied to a larger number of CSF samples may provide a better understanding of the cell-mediated immune response involved in NC.
Asunto(s)
Citometría de Flujo , Neurocisticercosis/líquido cefalorraquídeo , Neurocisticercosis/inmunología , Antígenos CD/análisis , Linfocitos B/clasificación , Linfocitos B/inmunología , Citometría de Flujo/métodos , Humanos , Células Asesinas Naturales/clasificación , Células Asesinas Naturales/inmunología , Neurocisticercosis/patología , Linfocitos T/clasificación , Linfocitos T/inmunologíaRESUMEN
The presence of phenotypically immature lymphocytes in umbilical cord blood has been a controversial topic. Moreover, their changes with age have not been systematically evaluated. In the present study, relative and absolute numbers of CD34+, CD10+CD19+, and CD4+CD8+ cell subsets were determined in umbilical cord blood from 12 full-term normal newborns, 43 children aged 1 month to 6 years, and 10 young adults. The samples were processed by whole-blood lysis and monoclonal antibody staining, and cells were analyzed by flow cytometry. Immature cells were present in cord blood and progressively declined in both absolute and percentage numbers with age, each according to a particular curve, reaching youth values roughly at age 2-4 years. These results demonstrate that phenotypically immature cells normally circulate at low levels in peripheral blood, mostly at birth and during infancy, but also during youth.
Asunto(s)
Linfocitos B/clasificación , Células Madre Hematopoyéticas/clasificación , Linfocitos T/clasificación , Adulto , Antígenos CD/análisis , Antígenos CD34/análisis , Linfocitos B/inmunología , Niño , Preescolar , Células Madre Hematopoyéticas/inmunología , Humanos , Inmunofenotipificación , Lactante , Recién Nacido , Linfocitos T/inmunologíaRESUMEN
Trypanosoma cruzi causes a profound immune depression in the infected host, and a small proportion of chagasic patients will develop a chronic disease characterized by myocardiopathy. There is evidence suggesting that dilated non-chagasic cardiomyopathy may be mediated by an immunological mechanism. In an attempt to distinguish abnormal immunoregulatory cell patterns in both dilated myocardiopathies, total and activated T and B lymphocyte subpopulations were measured by flow cytometry and double-labeling in whole blood samples from patients with dilated myocardiopathy, 10 with positive serological tests for T. cruzi and 9 with different non-chagasic cardiomyopathies. Several significant differences were found between both groups of patients and 13 sex- and age-matched apparently healthy controls. Chagasic patients besides showing clear decrease in absolute numbers of CD3+/CD71+ and CD8+/CD25+ cell populations also had a significant increase in CD19+, CD10+, and CD19+/HLA-DR+ cell subsets, as well as high helper/ suppressor cell ratio. These findings suggest that concurrently with T cell diminution, which involved activated T lymphocytes displaying suppressor/cytotoxic immunophenotype, chronic chagasic patients with myocardiopathy showed elevated numbers of total and activated B lymphocytes. Patients with dilated non-chagasic myocardiopathy had significantly increased numbers of activated T cells (CD3+/CD25+, CD8+/CD25+, and CD8+/HLA-DR+) and total and activated B lymphocytes (CD10+, CD19+, CD19+HLA-DR+). These data support the notion that dilated myocardiopathies other than the chagasics may be associated with immunological abnormalities.
Asunto(s)
Linfocitos B/inmunología , Cardiomiopatías/inmunología , Cardiomiopatía Chagásica/inmunología , Activación de Linfocitos , Linfocitos T/inmunología , Trypanosoma cruzi/inmunología , Adulto , Animales , Subgrupos de Linfocitos B/clasificación , Linfocitos B/clasificación , Cardiomiopatías/sangre , Cardiomiopatía Chagásica/sangre , Femenino , Humanos , Linfocitos/clasificación , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/clasificación , Linfocitos T/clasificaciónRESUMEN
Localized cutaneous leishmaniasis (LCL) in Colombia is caused primarily by Leishmania panamensis, a different species from those reported in Brazil, French Guiana, and Venezuela. Because different parasites may elicit disparate immune responses, the present study was undertaken to establish the leukocyte participation in the immune response against L. panamensis. Epidermal and dermal immune complexes were studied using an avidinbiotin immunoperoxidase technique and specific monoclonal antibodies. In LCL, the epidermis showed keratinocytes expressing intercellular adhesion molecule-1, a universal expression of human leukocyte antigen-DR, and a hyperplasia of CD1a+ Langerhans cells. The dermal granuloma observed had a mean +/- SEM value for the CD4/CD8 ratio of 0.80 +/- 0.06. The expression of the activation molecules CD25 (interleukin-2 receptor) and CD18 (lymphocyte function-associated antigen-1 beta), 10.5% and 38.1% respectively, suggests that many cells are primed and proliferating. Most T cells in the granuloma expressed alpha beta T cell receptor (TCR) (40.3%) whereas only a few (6.7%) expressed gamma delta TCR. The results show that Colombian LCL patients possessed the appropiate activation and accessory signals from immunocompetent cells to trigger the effector phase of the immune response and eventually eliminate the parasite.
Asunto(s)
Leishmania guyanensis/inmunología , Leishmaniasis Cutánea/inmunología , Piel/patología , Adulto , Animales , Anticuerpos Monoclonales/inmunología , Biopsia con Aguja , Femenino , Humanos , Inmunidad Celular , Técnicas para Inmunoenzimas , Inmunofenotipificación , Pruebas Intradérmicas , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/patología , Masculino , Piel/parasitología , Linfocitos T/clasificación , Linfocitos T/inmunologíaAsunto(s)
Linfocitos B/inmunología , Hormona del Crecimiento/efectos adversos , Linfocitos T/inmunología , Absentismo , Adolescente , Linfocitos B/clasificación , Niño , Preescolar , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/etiología , Femenino , Estudios de Seguimiento , Humanos , Recuento de Leucocitos , Masculino , Fitohemaglutininas , Estudios Prospectivos , Proteínas Recombinantes , Linfocitos T/clasificaciónRESUMEN
In this study, we assessed the proliferative response of T cells from mice chronically infected with Trypanosoma cruzi to actin, myosin, or T. cruzi soluble antigen (SA). We report here that CD4+ T cells from mice chronically infected with T. cruzi proliferated in response to myosin but not to actin, whereas cells from naive mice did not proliferate against any of the antigens tested. Antisera raised against myosin- or SA-activated T cells specifically inhibited respectively, the myosin or SA in vitro proliferative response, whereas the response to unrelated antigen remained unimpaired. Sera from chronically infected mice failed to show any significant inhibitory activity. The above findings suggest that autoreactive and T. cruzi-reactive T cells belong to different, perhaps nonoverlapping, compartments of the immune cell repertoire of mice chronically infected with T. cruzi. The failure of infected mice to trigger the suppressive mechanisms described here might be the primary immune defect leading to breakdown of self-tolerance and unopposed, perhaps tissue-damaging, autoimmunity in experimental Chagas' disease.
Asunto(s)
Antígenos de Diferenciación de Linfocitos T , Enfermedades Autoinmunes/inmunología , Enfermedad de Chagas/inmunología , Miosinas/inmunología , Linfocitos T/inmunología , Trypanosoma cruzi/inmunología , Adyuvantes Inmunológicos/inmunología , Animales , Antígenos de Protozoos/inmunología , Enfermedades Autoinmunes/sangre , Enfermedad de Chagas/sangre , Enfermedad Crónica , Epítopos/inmunología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Fenotipo , Factores Supresores Inmunológicos/sangre , Factores Supresores Inmunológicos/genética , Linfocitos T/clasificaciónRESUMEN
Fresh suspensions of tumor-infiltrating lymphocytes (TIL) from 16 patients with squamous cell carcinoma of the head and neck (SCCHN) were examined for T-cell markers including CD4 (helper-inducer), CD8 (cytotoxic-suppressor), natural killer (NK) cell, and activation surface markers using monoclonal antibodies and two-color flow cytometry. Two of 8 (25%) patients with a CD4/CD8 ratio of less than 1 developed cervical lymph node metastases; none had extracapsular spread. Six of 8 (75%) patients with a CD4/CD8 ratio of greater than 1 developed cervical metastases; 5 of 6 (83%) exhibited extracapsular spread. An increased CD4/CD8 ratio was attributable to a decrease in CD8+ cells. A CD4/CD8 ratio of greater than 1 may be a useful prognostic indicator of the development of cervical metastases.
Asunto(s)
Carcinoma de Células Escamosas/inmunología , Neoplasias de Cabeza y Cuello/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Anticuerpos Monoclonales/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Antígenos CD8 , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T/clasificaciónRESUMEN
We recently described the induction of an inflammatory myopathy in SJL/J mice after injection of skeletal muscle Ag and adjuvant that is characterized by necrosis of muscle fibers associated with infiltrating mononuclear cells. In the present study, an immunohistologic analysis was performed to examine the phenotype of these infiltrating cells and to determine changes in cell-surface Ag expression in involved muscle. The predominant cells infiltrating muscle after induction of experimental autoimmune myositis (EAM) were found to be Mac-1+/I-A+ macrophages, representing 80 to 90% of all infiltrating cells, and CD4+ T lymphocytes, representing 10 to 15% of all infiltrating cells. Few CD8+ T cells, and no B cells, were seen in the involved muscles. Interestingly, endothelial cells in involved muscles were also noted to express class II MHC Ag. Aberrant I-A Ag expression was not observed on endothelial cells in other tissues examined, including kidney, liver, cardiac muscle, and lung. I-A Ag expression appeared to correlate with susceptibility to disease in that muscle endothelial cells remained negative after attempts to induce EAM in a nonsusceptible strain. Together, the data suggest that aberrant organ-specific class II MHC Ag expression and a response by CD4+ T cells may be pathogenetically involved in the muscle injury of EAM. In addition, the predominance of infiltrating macrophages suggests that these recruited cells may also be important in the immune-mediated muscle damage.