Antigen-stimulated apoptotic T cell death: a model for CD4+ T cell depletion in HIV-1 infection.
Int Conf AIDS 1996 Jul 7-12; 11:15 (abstract no. We.A.501) Shearer GM; Exptl. Immunol. Branch, NCI, NIH, Bethesda, MD, USA. Fax: 301-496-0887.
Apoptotic T cell death has been suggested to contribute to the depletion of CD4+ T lymphocytes characteristic of progression to AIDS. However, both CD4+ and CD8+ T cell exhibit apoptotic death, either without stimulation or when stimulated via pan-T cell receptor signaling. Thus, both subsets appear to be activated to die upon further stimulation. Because HIV-infected individuals are likely to be infected with specific antigens, many of which are CD4-dependent, our laboratories tested the possibility that CD4+ T cells will be the dominant subset to die upon stimulation with CD4-dependent antigens such as influenza A virus or HIV-1 envelope peptides. We observed that: 1) stimulation with these antigens resulted in selective death of the CD4+ T cells in patients with CD4 counts greater than 300/microliter; 2) death could be reduced by addition of IL-2, IL-12, IFN-y, or anti-IL-4 and IL-10 to the cultures; 3) death occurred later in cultures stimulated with antigens than with pan-T cell stimulation; and 4) death was due to a soluble factor that was blocked by anti-lymphotoxin but not by anti-FAX (Clerici et al. AIDS in press). This model may approximate the conditions seen in vivo in progression to AIDS, and suggests that T cell activation by HIV-1 and/or its products is a critical initial step in depletion of CD4+ T cells.
Keywords: AEGIS, Antigens, CD4, HIV Infections, CD4-Positive T-Lymphocytes, HIV-1, Cell Death, Antigens, CD8, Acquired Immunodeficiency Syndrome, T-Lymphocytes, Receptors, Antigen, T-Cell, Apoptosis, Simian Acquired Immunodeficiency Syndrome, Human, ICA11
