RESUMO
Peripheral blood mononuclear cells with T(FH) phenotype from two asymptomatic XLP patients were studied. Normal/high numbers of CXCR5+, CD4+ T cells coexpressing PD-1 were demonstrated. Peripheral blood mononuclear cells (PBMC) from these patients responded to sub-optimal PHA/IL-2 stimulation upregulating ICOS and CD40L and increasing intracellular expression of IL-10, IL-21 and IL-4 by CD4+ T(FH) cells. However when compared to N, the time profile of activation and cytokine synthesis was different in XLP and N. While ICOS and CD40L expression in N decreased after 6-8 days, it continued to increase or was maintained in XLP cultures. Intracellular IL-10, IL-21 and IL-4 reached higher values in XLP than N after 8 days. Rather than the absence of T(FH) cells or their intrinsic inability to respond to stimuli, differences in the time profile of their response could contribute to impair their role as helpers of B lymphocytes.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Transtornos Linfoproliferativos/imunologia , Adulto , Linfócitos T CD4-Positivos/efeitos dos fármacos , Ligante de CD40/biossíntese , Ligante de CD40/imunologia , Células Cultivadas , Éxons , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Proteína Coestimuladora de Linfócitos T Induzíveis/biossíntese , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Interleucina-2/imunologia , Interleucina-2/farmacologia , Interleucinas/imunologia , Interleucinas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucócitos Mononucleares/imunologia , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/genética , Pessoa de Meia-Idade , Mutação , Fito-Hemaglutininas/imunologia , Fito-Hemaglutininas/farmacologia , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária , Linfócitos T Auxiliares-Indutores/imunologia , Regulação para Cima/imunologiaRESUMO
Expression of the activation antigen CD38 on T cells is a strong predictor of the risk of HIV disease progression, but it is not known whether CD38 is a marker or mediator of dysfunction. We examined the relationship between CD38 expression and responses to T-cell receptor stimulation in central memory and effector memory CD4 T cells in HIV-infected persons and in healthy controls. Basal CD38 expression was preserved by blocking golgi transport with brefeldin A. Intracellular expression of interleukin 2, interferon γ, and CD154 was measured after stimulating peripheral blood mononuclear cells with the superantigen staphylococcal enterotoxin B with or without anti-CD28 costimulation. Interferon-γ responses were comparable or increased in stimulated CD38 memory cells, and the interleukin 2 responses of costimulated CD38 central memory cells were decreased in HIV infection. In CD38 cells and especially in CD38 cells of HIV-infected persons, stimulated memory cells more often failed to express CD154 (CD40 ligand) when induced to express cytokine. A dissociated cytokine and CD154 expression by memory CD4 T cells may impair interactions between T cells and antigen-presenting cells, contribute to impaired immunity and help explain the relationship between CD38 expression and disease progression in chronic HIV infection.