Cytokines in immune regulation/pathogenesis in HIV infection.

G. M. Shearer, M. Clerici, A. Sarin, J. A. Berzofsky, P. A. Henkart

Research output: Contribution to journalArticle

Abstract

Two hallmarks of immunopathogenesis in the progression of HIV-infected individuals to AIDS are the loss of T helper (Th) cell function in response to antigens and the critical reduction in CD4+ T cell numbers. It is probable that these two phenomena are related. We observed that: (1) the failure to detect antigen-stimulated Th cell responses in vitro correlates with increased pokeweed mitogen/staphylococcal enterotoxin B (P/S)-stimulated and antigen-stimulated T cell death; and (2) both of these events are similarly modulated by immunoregulatory cytokines. Interleukin 2 (IL-2) and IL-12 (Th1-type cytokines), as well as antibodies to IL-4 and IL-10 (which are Th2-type cytokines) restore in vitro Th cell responses to recall antigens such as influenza virus and HIV envelope synthetic peptides (env). P/S-induced T cell death affects both CD4+ and CD8+ T cell subsets, whereas death induced by stimulation with env affects only CD4+ T cells. In both examples, Th1-type cytokines and antibodies to Th2-type cytokines protect against T cell death. In contrast, IL-4 and IL-10 do not protect against death, and anti-IL-12 antibody can enhance T cell death. Our findings indicate that the loss of Th cell function and increased T cell death seen in vitro are correlated, and that in vivo HIV infection gives rise to inappropriate cytokines resulting in immune dysfunction and immunopathogenesis.

Original languageEnglish
JournalCiba Foundation symposium
Volume195
Publication statusPublished - 1995

ASJC Scopus subject areas

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    Shearer, G. M., Clerici, M., Sarin, A., Berzofsky, J. A., & Henkart, P. A. (1995). Cytokines in immune regulation/pathogenesis in HIV infection. Ciba Foundation symposium, 195.