Differential Priming to Programmed Cell Death of Superantigen-Reactive Lymphocytes of HIV Patients

Abstract

Programmed cell death or apoptosis has been shown to play a central role in CD4⁺ T cell depletion following HIV infection. Because most apoptotic signals are delivered through T cell receptor stimulation, we investigated whether T cell depletion in AIDS is a stochastic phenomenon or if it preferentially affects T cell subsets defined by their interaction with superantigens. To address this problem we have taken advantage of the exclusive property of superantigens to trigger T cells expressing selective sets of T cell receptor Vβ elements. Here we report that CD4⁺ T cells from HIV-infected patients can proliferate in vitro to T cell receptor mobilization by some superantigens, but not others. Furthermore, the failure of T cells to respond to some superantigens was shown to be due to an active cell death process that differentially affected T cells capable of interacting with different superantigens.

The selective programmed cell death priming of T cells responsive to particular superantigens, observed in this study, suggests that T cell depletion in HIV infection is not simply due to the cytopathic effect of the virus. The possible link between programmed cell death and T cell receptor variable regions suggested by the present experiments may help to better define current models of AIDS pathogenesis.