The T Helper Cell Shift in AIDS: Significance for Pharmacotherapy

We recently postulated that susceptibility to HIV infection and progression of HIV-infected individuals to AIDS is controlled by cytokines that regulate 2 functionally distinct subsets of T helper (T_H) lymphocytes. These subsets are T_H1, which mainly enhance cell-mediated immunity and are regulated by type 1 cytokines. and T_H2, which mainly augment antibody production and are regulated by type 2 cytokines. HIV-seronegative individuals exposed to HIV may exhibit strong HIV-specific T cell-mediated immunity, since both HIV-specific T helper and T cytotoxic lymphocytes are activated in the absence of seroconversion and disease. Additionally, during progression of HIV-seropositive individuals to AIDS. a decline is observed in type 1 cytokines as well as an increase in the production of type 2 cytokines by HIV-positive peripheral blood mononuclear cells stimulated in vitro. The type 1 to type 2 switch is predictive for the following clinically relevant events: (a) reduction in CD4+ cell counts; (b) time to diagnosis of AIDS; and (c) time to death. The manipulation of the immune response to induce and strengthen HIV-specific immunity may thus be useful in the management of HIV infection.