INTERFERON-ALPHA AND TAT INVOLVEMENT IN THE IMMUNOSUPPRESSION OF UNINFECTED T-CELLS AND C-C CHEMOKINE DECLINE IN AIDS

HIV type 1 (HIV-1) not only directly kills infected CD4(+) T cells but also induces immunosuppression of uninfected T cells, Two immunosuppr essive proteins, interferon alpha (IFN alpha) and extracellular Tat, m ediate this process because specific antibodies against these proteins prevent generation of suppressor cells in HIV 1-infected peripheral b lood mononuclear cell cultures, Furthermore, the production of C-C che mokines in response to immune cell activation, initially enhanced by I FN alpha and Tat, ultimately is inhibited by these proteins in paralle l with their induction of immunosuppression, The clinical corollary is the immunosuppression of uninfected T cells and the decline in C-C ch emokine release found at advanced stages of HIV-1 infection parallelin g rising levels of IFN alpha and extracellular Tat, We, therefore, sug gest that IFN alpha and Tat may be critical targets for anti-AIDS stra tegies.