Interferon α and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS |
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Authors: | Daniel Zagury Abderrahim Lachgar Vida Chams Lat S Fall Jacky Bernard Jean-Franois Zagury Bernard Bizzini Alessandro Gringeri Elena Santagostino Jay Rappaport Michael Feldman Arsne Burny and Robert C Gallo |
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Institution: | Daniel Zagury, Abderrahim Lachgar, Vida Chams, Lat S. Fall, Jacky Bernard, Jean-François Zagury, Bernard Bizzini, Alessandro Gringeri, Elena Santagostino, Jay Rappaport, Michael Feldman, Arsène Burny, and Robert C. Gallo |
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Abstract: | HIV type 1 (HIV-1) not only directly kills infected CD4+ T cells but also induces immunosuppression of uninfected T cells. Two immunosuppressive proteins, interferon α (IFNα) and extracellular Tat, mediate this process because specific antibodies against these proteins prevent generation of suppressor cells in HIV-1-infected peripheral blood mononuclear cell cultures. Furthermore, the production of C-C chemokines in response to immune cell activation, initially enhanced by IFNα and Tat, ultimately is inhibited by these proteins in parallel with their induction of immunosuppression. The clinical corollary is the immunosuppression of uninfected T cells and the decline in C-C chemokine release found at advanced stages of HIV-1 infection paralleling rising levels of IFNα and extracellular Tat. We, therefore, suggest that IFNα and Tat may be critical targets for anti-AIDS strategies. |
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