The SIV/macaque model was employed to determine whether superantigen-mediated activation of the immune system, which may occur as a result of certain superimposed bacterial or viral infections in HIV-infected humans, can play a role in the immunopathogenesis of AIDS. Rhesus monkeys were inoculated with a defined superantigen, staphylococcal enterotoxin B (SEB), and assessed both for clinical outcome, and for virologic and immunologic events in PBL and lymphoid tissues. T cell receptor (TCR) Va repertoire studies in five uninfected monkeys using flow cytometry and PCR-based quantitation techniques demonstrated that SEB potently stimulated the transient expansion of both CD4+ and CD8+ T lymphocyte subpopulations expressing members of TCR Va 3, Va 14, Va 15, Va 17 and Va19 gene families. Eight similarly inoculated SIVmac-infected monkeys, however, exhibited a strikingly different response to the SEB superantigen. Their CD8+ lymphocyte subpopulations expressing members of the Va 3, Va 14, Va 15, Va 17 and Va19 gene families demonstrated prolonged activation and expansion in PBL following SEB inoculation. The responding CD8+ cell populations could be detected up to three weeks after SEB injection. In contrast, CD4+ lymphocyte subpopulations expressing members of those selected Va gene families displayed either a subtle or no detectable expansion in PBL of four SIVmac-infected animals in response to SEB. Interestingly, TUNEL analyses revealed numerous apoptotic lymphocytes in lymphoid tissues obtained on day 1 post-SEB injection in the animals. Furthermore, three of the eight chronically SIVmac-infected monkeys died 1,5 and 9 weeks following the SEB injection. Further studies are ongoing to determine whether SEB-induced activation is associated with an increased viral load in those animals. The present studies suggest that CD4+ T lymphocytes of SIVmac-infected monkeys may be predisposed to apoptosis and/or anergy in response to superantigens. The persistent infection of monkeys with SIVmac can also be predisposed to exaggerated reaction of CD8+ lymphocytes to bacterial superantigens. Thus, bacterial superantigens may contribute to disease progression in AIDS virus-infected individuals.
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