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Frequency and cytokine profile of HPRT mutant T cells in HIV-infected and healthy donors: implications for T cell proliferation in HIV disease.
Paganin, C; Monos, D S; Marshall, J D; Frank, I; Trinchieri, G.
Afiliação
  • Paganin C; Wistar Institute of Anatomy and Biology, University of Pennsylvania, Philadelphia 19104, USA.
J Clin Invest ; 99(4): 663-8, 1997 Feb 15.
Article em En | MEDLINE | ID: mdl-9045868
It has been postulated that HIV-infected patients undergo an active production of virus and CD4+ T cell destruction from the early stages of the disease, and that an extensive postthymic expansion of CD4+ T cells prevents a precipitous decline in CD4+ T cell number. Based on the rebound of the CD4+ T cell number observed in patients undergoing antiretroviral therapy with protease inhibitors, it has been calculated that, on average, 5% of T cells are replaced every day in HIV-infected patients. To obtain an independent estimate of the recycling rate of T cells in the patients, we measured the frequency of cells carrying a loss-of-function mutation at the hypoxanthine guanine phosphoribosyl transferase (hprt) locus. Assuming a recycling rate of 5%/d, an accumulation of 2.6 mutations/10(6)/yr over the physiological accumulation was predicted. Indeed, we observed an elevated frequency of HPRT mutants in the CD4+ T cells of most patients with < 300 CD4+ T cells/mm3 of blood and in the CD8+ T cells of most patients with < 200 CD4+ T cells/mm3, consistent with an elevated and protracted increased division rate in both subsets. However, in earlier stages of the disease the mutant frequency in both CD4+ and CD8+ T cells was lower than in healthy controls. The cytokine production profile of most HPRT mutant CD4+ T cell clones from both healthy and HIV-infected patients was typical of T helper cells type 2 (high IL-4 and IL-10, low IFN-gamma), whereas the cytokine production pattern of wild-type clones was heterogeneous. The cytokine profile of CD8+ clones was indistinguishable between HPRT mutants and wild type. Our data provide evidence of increased CD4+ and CD8+ T cell recycling in the HIV-infected patients.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Ativação Linfocitária / Linfócitos T CD4-Positivos / Infecções por HIV / Citocinas / Hipoxantina Fosforribosiltransferase Tipo de estudo: Prognostic_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Invest Ano de publicação: 1997 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Ativação Linfocitária / Linfócitos T CD4-Positivos / Infecções por HIV / Citocinas / Hipoxantina Fosforribosiltransferase Tipo de estudo: Prognostic_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Invest Ano de publicação: 1997 Tipo de documento: Article