VIRAL SUPERANTIGEN-INDUCED HYPORESPONSIVENESS OF T-CELLS AND POLYCLONAL B-CELL ACTIVATION IN HIV-1 INFECTION

The mechanisms of CD4 depletion and hyporesponsiveness during human im munodeficiency virus (HIV) infection are still unknown. Given the abil ity of superantigens to stimulate a higher number of lymphocytes than conventional antigens, they may play a major role in this process. Rec ently, a novel superantigen, the rabies virus nucelocapsid (NC), was d escribed in humans. In the present work, we tested the responses of pe ripheral blood lymphocytes from asymptomatic HIV-infected patients to this superantigen, the rabies virus nucleocapsid (NC), was described i n humans. In the present work, we tested the responses of peripheral b lood lymphocytes from asymptomatic HIV-infected patients to this super antigen. In contrast to its effect in normal controls, NC failed to ex pand T cells from HIV-infected individuals expressing the V beta 8 fam ily, and induced a strong decrease in the response to CD3 activation. This absence of response was not the consequence of programmed cell de ath, and was explained by an anergic state induced by the superantigen . NC superantigen was also able to induce polyclonal activation of B c ells, as measured by the secretion of anti-HIV antibodies and autoanti bodies. Moreover, V beta 8 depletion experiments showed that induction of autoantibody secretion was V beta 8 dependent, whereas secretion o f HIV-1 antibody was not. Interleukin secretion studies showed that NC was able to induce high levels of interleukin-4 and interleukin-10. T aken together, our results suggest a role for exogenous viral superant igens such as NC in the induction of T cell hyporesponsiveness and pol yclonal B cell activation during HIV infection. The induction of a T(h )2 response and the role of these superantigens in the immunopathogene sis of acquired immunodeficiency syndrome are discussed.