Cytokines in immune regulation/pathogenesis in HIV infection.
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.
Shearer
G M
GM
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Clerici
M
M
Sarin
A
A
Berzofsky
J A
JA
Henkart
P A
PA
D016207:Cytokines / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines