Evidence for an in vivo superantigenic activity in human immunodeficiency virus-infected individuals

In a previous study, we reported the existence of a specific anergy affecting selectively the V beta 8 subset in both CD4 and CD8 T cells from human immunodeficiency virus (HIV)-infected persons. Because this observation gives evidence for a previous in vivo activation of this subset by a superantigen, we further characterize, in the present study, this V beta 8-anergy associated with HIV infection. Molecular T cell receptor analysis indicates that the V beta 8-anergized T cells are polyclonal. Furthermore, we show the dependence of this anergy on the expression of allelic forms of HLA class II DRB1 molecules. These observations explain the frequency of anergic persons among HIV-infected donors (56%) and are consistent with a previous in vivo superantigenic activity. Comparative analyses of disease evolution between V beta 8 responder and anergic persons do not show any clear relation between the V beta 8 status and acquired immunodeficiency syndrome pathogenesis. However, the stability of the V beta 8 status, the absence of correlation with previous microbial infections, and the previously reported precocity of V beta 8 anergization are in favor of a strong association between the in vivo existence of a V beta 8-specific superantigen and HIV infection. Finally, the functional dichotomy we observe for all anergized donors between blood and lymph node T cells raises the question of the in vivo localization of the superantigenic activity.