RESUMEN
The circulating precursor cells that give rise to human resident memory T cells (TRM) are poorly characterized. We used an in vitro differentiation system and human skin-grafted mice to study TRM generation from circulating human memory T cell subsets. In vitro TRM differentiation was associated with functional changes, including enhanced IL-17A production and FOXP3 expression in CD4+ T cells and granzyme B production in CD8+ T cells, changes that mirrored the phenotype of T cells in healthy human skin. Effector memory T cells (TEM) had the highest conversion rate to TRM in vitro and in vivo, but central memory T cells (TCM) persisted longer in the circulation, entered the skin in larger numbers, and generated increased numbers of TRM. In summary, TCM are highly efficient precursors of human skin TRM, a feature that may underlie their known association with effective long-term immunity.
Asunto(s)
Linfocitos T CD8-positivos , Memoria Inmunológica , Animales , Humanos , Células T de Memoria , Ratones , Piel , Subgrupos de Linfocitos TRESUMEN
Doxycycline-induced liver injury is a rare phenomenon, with an unclear clinical course and etiopathogenesis. The onset of injury may be acute-to-subacute, with a pattern ranging from hepatocellular or cholestatic to mixed, and it often lasts up to several weeks. We present a case of cholestatic liver injury secondary to doxycycline use in a middle-aged woman. In patients with a history of doxycycline exposure and subsequent hepatic injury, an adverse drug reaction due to doxycycline should remain on the differential, and immediate removal of the offending agent with close monitoring of the clinical condition should be pursued.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Colestasis , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Colestasis/inducido químicamente , Doxiciclina/efectos adversos , Femenino , Humanos , Hígado , Persona de Mediana EdadRESUMEN
PURPOSE: We report a case a pediatric patient with an eyelid lesion found to be a basaloid follicular hamartoma. OBSERVATIONS: A six-year-old female with juvenile diabetes who presented with a benign eyelid lesion harboring an aberrant eyelash. CONCLUSIONS AND IMPORTANCE: Basaloid follicular hamartoma is a rare benign neoplasm arising from hair follicles. These lesions can resemble basal cell carcinomas and require complete excision.
RESUMEN
Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19.
Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/diagnóstico , Inmunoensayo/métodos , Técnicas de Diagnóstico Molecular/métodos , Neumonía Viral/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Pruebas Serológicas/métodos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , COVID-19 , Infecciones por Coronavirus/sangre , Humanos , Inmunoensayo/normas , Técnicas de Diagnóstico Molecular/normas , Pandemias , Neumonía Viral/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , SARS-CoV-2 , Sensibilidad y Especificidad , Pruebas Serológicas/normasRESUMEN
OBJECTIVE: To review cases and increase awareness in clinicians treating patients who may be taking biotin. METHODS: We describe the presentation and workup of a woman with secondary progressive multiple sclerosis on high dose biotin with laboratory studies suggestive of thyrotoxicosis. RESULTS: Plasma samples showed laboratory evidence of elevated thyroid hormone levels with elevated free thyroxine >7.8 ng/dl (reference interval (RI) 0.9-1.7 ng/dl) and decreased thyroid stimulating hormone <0.02 uIU/ml (RI 0.50-5.70 uIU/ml). Laboratory values normalized when biotin was withheld prior to repeat testing. CONCLUSIONS: Our case report demonstrates that ingestion of high dose biotin in multiple sclerosis patients can cause interference with laboratory assessment of thyroid function. This interference causes laboratory values suggestive of thyrotoxicosis and can lead to unnecessary evaluation. Clinicians should be aware of the risk of laboratory interference in this patient demographic.
RESUMEN
PURPOSE: In leukemic cutaneous T-cell lymphoma (L-CTCL), malignant T cells accumulate in the blood and give rise to widespread skin inflammation. Patients have intense pruritus, increased immunoglobulin E (IgE), and decreased T-helper (TH)-1 responses, and most die from infection. Depleting malignant T cells while preserving normal immunity is a clinical challenge. L-CTCL has been variably described as a malignancy of regulatory, TH2 and TH17 cells. EXPERIMENTAL DESIGN: We analyzed phenotype and cytokine production in malignant and benign L-CTCL T cells, characterized the effects of malignant T cells on healthy T cells, and studied the immunomodulatory effects of treatment modalities in patients with L-CTCL. RESULTS: Twelve out of 12 patients with L-CTCL overproduced TH2 cytokines. Remaining benign T cells were also strongly TH2 biased, suggesting a global TH2 skewing of the T-cell repertoire. Culture of benign T cells away from the malignant clone reduced TH2 and enhanced TH1 responses, but separate culture had no effect on malignant T cells. Coculture of healthy T cells with L-CTCL T cells reduced IFNγ production and neutralizing antibodies to interleukin (IL)-4 and IL-13 restored TH1 responses. In patients, enhanced TH1 responses were observed following a variety of treatment modalities that reduced malignant T-cell burden. CONCLUSIONS: A global TH2 bias exists in both benign and malignant T cells in L-CTCL and may underlie the infectious susceptibility of patients. TH2 cytokines from malignant cells strongly inhibited TH1 responses. Our results suggest that therapies that inhibit TH2 cytokine activity, by virtue of their ability to improve TH1 responses, may have the potential to enhance both anticancer and antipathogen responses.
Asunto(s)
Interleucina-13/fisiología , Interleucina-4/fisiología , Linfoma Cutáneo de Células T/inmunología , Neoplasias Cutáneas/inmunología , Células TH1/inmunología , Células Th2/metabolismo , Anciano , Anciano de 80 o más Años , Técnicas de Cocultivo , Femenino , Humanos , Linfoma Cutáneo de Células T/patología , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/patología , Carga Tumoral , Células Tumorales CultivadasRESUMEN
Merkel cell carcinomas (MCCs) are rare but highly malignant skin cancers associated with a recently described polyomavirus. MCC tumors were infiltrated by T cells, including effector, central memory, and regulatory T cells. Infiltrating T cells showed markedly reduced activation as evidenced by reduced expression of CD69 and CD25. Treatment of MCC tumors in vitro with IL-2 and IL-15 led to T-cell activation, proliferation, enhanced cytokine production, and loss of viable tumor cells from cultures. Expanded tumor-infiltrating lymphocytes showed TCR repertoire skewing and upregulation of CD137. MCC tumors implanted into immunodeficient mice failed to grow unless human T cells in the tumor grafts were depleted with denileukin diftitox, suggesting that tumor-specific T cells capable of controlling tumor growth were present in MCC. Both CD4(+) and CD8(+) FOXP3(+) regulatory T cells were frequent in MCC. Fifty percent of nonactivated T cells in MCC-expressed PD-1, a marker of T-cell exhaustion, and PD-L1 and PD-L2 were expressed by a subset of tumor dendritic cells and macrophages. In summary, we observed tumor-specific T cells with suppressed activity in MCC tumors. Agents that stimulate T-cell activity, block regulatory T cell function, or inhibit PD-1 signaling may be effective in the treatment of this highly malignant skin cancer.
Asunto(s)
Carcinoma de Células de Merkel/patología , Receptor de Muerte Celular Programada 1/metabolismo , Neoplasias Cutáneas/patología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología , Linfocitos T/metabolismo , Linfocitos T/patología , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Antígenos CD8/metabolismo , Carcinoma de Células de Merkel/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Factores de Transcripción Forkhead/metabolismo , Humanos , Técnicas In Vitro , Interleucina-15/farmacología , Interleucina-2/farmacología , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Lectinas Tipo C/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones SCID , Transducción de Señal/fisiología , Piel/metabolismo , Piel/patología , Neoplasias Cutáneas/metabolismo , Linfocitos T/efectos de los fármacos , Trasplante HeterólogoRESUMEN
BACKGROUND: Roughly, 10% of elderly patients develop postoperative cognitive dysfunction. General anesthesia impairs spatial memory in aged rats, but the mechanism is not known. Hippocampal neurogenesis affects spatial learning and memory in rats, and isoflurane affects neurogenesis in neonatal and young adult rats. We tested the hypothesis that isoflurane impairs neurogenesis and hippocampal function in aged rats. METHODS: Isoflurane was administered to 16-month-old rats at one minimum alveolar concentration for 4 h. FluoroJade staining was performed to assess brain cell death 16 h after isoflurane administration. Dentate gyrus progenitor proliferation was assessed by bromodeoxyuridine injection 4 days after anesthesia and quantification of bromodeoxyuridine+ cells 12 h later. Neuronal differentiation was studied by determining colocalization of bromodeoxyuridine with the immature neuronal marker NeuroD 5 days after anesthesia. New neuronal survival was assessed by quantifying cells coexpressing bromodeoxyuridine and the mature neuronal marker NeuN 5 weeks after anesthesia. Four months after anesthesia, associative learning was assessed by fear conditioning. Spatial reference memory acquisition and retention was tested in the Morris Water Maze. RESULTS: Cell death was sporadic and not different between groups. We did not detect any differences in hippocampal progenitor proliferation, neuronal differentiation, new neuronal survival, or in any of the tests of long-term hippocampal function. CONCLUSION: In aged rats, isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome.