Artigo Revisado por pares

Glucocorticoids rescue CD4+ T lymphocytes from activation-induced apoptosis triggered by HIV-1

1995; Lippincott Williams & Wilkins; Volume: 9; Issue: 1 Linguagem: Inglês

10.1097/00002030-199501000-00005

ISSN

1473-5571

Autores

Wei Lu, Rosângela Salerno-Gonçalves, Ju Yuan, Doré Sylvie, Dai Shu Han, Jean Marie Andrieu,

Tópico(s)

Immunotherapy and Immune Responses

Resumo

Objective During HIV-1 infection, CD4+ T lymphocytes migrate to immune-reactive lymphoid organs where they are infected by the virus and/or killed by apoptosis on immunoregulatory stimuli—a potential mechanism underlying fatal CD4+ T-cell depletion observed in AIDS. This study seeks to determine the effects of glucocorticoids (GCC) on the activation-induced T-cell apoptosis triggered by HIV-1. Methods CD4+ and CD8+ T cells were purified from HIV-negative donor peripheral blood mononuclear cells (PBMC) by positive selection and exposed to HIV-1 (primary isolates). HIV-1-exposed CD4+ and CD8+ T cells as well as PBMC derived from HIV-1-infected patients were cultured with medium alone or anti-CD3 monoclonal antibodies (MAb)/mitogens in the presence or absence of hydrocortisone or prednisolone. Viral infection kinetics were assessed by polymerase chain reaction and viral replication was measured by p24 enzyme-linked immunosorbent assay. Cell survival, apoptosis, T-cell proliferation, blast cell transformation, and interleukin (IL)-2 receptor (CD25) expression were monitored in parallel for each cell population. Results Fractionated CD4+ T cells acutely infected by HIV-1 underwent apoptotic death on anti-CD3 MAb/mitogen stimulation. This activation-induced apoptotic cell killing was antagonized by pharmacological doses of prednisolone or hydrocortisone added up to 6 h after stimulation. GCC were also found to be capable of inhibiting the accelerated apoptosis in PBMC (including both CD4+ and CD8+ T-cell fractions) from HIV-1-infected patients. This anti-apoptotic action of GCC overbalanced their downregulatory effect on T-cell proliferation, resulting in an overall improvement of CD4+ T-cell survival in patient PBMC. These effects of GCC were abrogated by the anti-GCC RU486 and were not associated with significant suppression of CD25 expression and IL-2-dependent T-cell blast transformation; moreover, GCC had no impact on viral infection and replication. Conclusion GCC exert a receptor-mediated anti-apoptotic activity in mature T cells through both activation-induced and HIV-1-triggered pathways, and could be potent inhibitors of T-cell apoptosis in HIV-1-infected patients.

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