Differential priming to programmed cell death of superantigen-reactive lymphocytes of HIV patients.
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 V beta 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.
Gorla
R
R
Clinical Immunology Units, Spedali Civili of Brescia, Italy.
Imberti
L
L
Prati
E
E
Brugnoni
D
D
Caligaris
S
S
Cattaneo
R
R
Albertini
A
A
Primi
D
D
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006679:HIV Seropositivity / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D011948:Receptors, Antigen, T-Cell; D018089:Superantigens