Assuntos
Bioensaio , Quimiocinas CC/análise , Dosagem de Genes , Síndrome da Imunodeficiência Adquirida/genética , Algoritmos , Terapia Antirretroviral de Alta Atividade , Estudos de Casos e Controles , Quimiocinas CC/genética , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 3 , Análise por Conglomerados , Estudos de Coortes , DNA/genética , DNA/isolamento & purificação , Sondas de DNA/química , Diabetes Mellitus Tipo 1/genética , Progressão da Doença , Etnicidade/genética , Predisposição Genética para Doença , Variação Genética , Genótipo , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Ligantes , Reação em Cadeia da Polimerase/métodos , Grupos Populacionais/genética , Receptores CCR5/genética , Padrões de Referência , Reprodutibilidade dos Testes , Sequências Repetidas Terminais/genética , Reino UnidoRESUMO
BACKGROUND: Despite suppression of the human immunodeficiency virus type 1 (HIV-1) load by highly active antiretroviral therapy (HAART), recovery of CD4+ T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to gamma-chain (gammac) cytokines known to influence T cell homeostasis. METHODS: The responsiveness of T cells to interleukin (IL)-2, IL-7, and IL-15 was determined by assessing cytokine-induced phosphorylation of the signal transducer and activator of transcription 5 (STAT5) in peripheral T cells obtained from 118 HIV-positive subjects and 13 HIV-negative subjects. RESULTS: The responsiveness of T cells to interleukin (IL)-7 but not to IL-2 or IL-15 was lower among HIV-positive subjects than among HIV-negative subjects. Among subjects with viral load suppression, the degree of IL-7 responsiveness (1) correlated with naive CD4+ T cell counts and was a better immune correlate of the prevailing CD4+ T cell count than were levels of human leukocyte antigen-DR1 or programmed death-1, which are predictors of T cell homeostasis during HIV infection; and (2) was greater in subjects with complete (i.e., attainment of >or=500 CD4+ T cells/mm3>or=5 years after initiation of HAART) versus incomplete immunologic responses. The correlation between plasma levels of IL-7 and CD4+ T cell counts during HAART was maximal in subjects with increased IL-7 responsiveness. CONCLUSIONS: Responsiveness of T cells to IL-7 is associated with higher CD4+ T cell counts during HAART and thus may be a determinant of the extent of immune reconstitution.