Identification of a CD28-mediated antiviral effect that is independent of CD8 cells.
Int Conf AIDS 1996 Jul 7-12; 11:15 (abstract no. We.A.405) Levine BL, Mosca J, Riley J, Carroll R, Vahey M, Jagodzinski L, Wagner K, Mayers D, Burke D, Weislow O, St Louis D, June C; NMRI, Tissue Bank, Bethesda, MD. Fax: 301-295-6857. E-mail: rin0bll@bumed30.med.navy.mil.
Human immunodeficiency virus type 1 (HIV-1) infection is associated with a progressive decline in CD4+ lymphocytes. Because stimulation of CD4+ lymphocytes leads to activation of HIV-1 replication, viral spread and cell death, adoptive CD4+ cell therapy has not been possible. We report here that CD28 receptor costimulation can lead to polyclonal expansion of CD4+ cells from HIV-infected donors during cell culture. Activated cells secreted predominately cytokines associated with T helper type 1 function. HIV-1 specific expression and proviral DNA load declined during culture. Surprisingly, the addition of antiretroviral agents to cell cultures was not required. Moreover, CD28 stimulation rendered CD4+ T cells from uninfected donors highly resistant to HIV-1 infection. The mechanism responsible for the anti-HIV effect was related to the mode of T cell activation by anti-CD28. The effect was independent of CD8+ T cells, and while CD4+ T cells stimulated with immobilized anti-CD28 were resistant to HIV infection, cells stimulated with soluble anti-CD28 were highly susceptible to HIV infection. CD4+ T cells stimulated by anti-CD28 secrete RANTES, MIP-la and MIP-lb. Preliminary experiments, however, indicate that the secretion of these chemokines is not sufficient for inhibition of HIV mediated by anti-CD28, as stimulation conditions that were permissive for virus also induced secretion of these chemokines. The CD28-mediated antiviral effect occurred early in the viral life cycle, prior to HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.
Keywords: AEGIS, Antigens, CD28, Antigens, CD8, HIV-1, CD4-Positive T-Lymphocytes, HIV Infections, Antiviral Agents, Virus Replication, Antigens, CD4, T-Lymphocytes, Chemokines, Cytokines, Human, virology, ICA11
