Selective Anergy of + T Cells in Human

We have analyzed the V/~ usage by CD4 + and CD8 + T cells from human immunodeficiency virus (HIV)-infected individuals in response to an in vitro stimulation with the superantigenic erythrogenic toxin A (ETA) of Streptococcus ivogenes. ETA amplifies specifically CD4 + and CD8 + T ceils from control donors expressing the V~8 and the VB12 dements. When peripheral T ceils from asymptomatic HIV-infected individuals were stimulated with ETA, there was a complete lack of activation of the V/~8 + T cell subset, whereas the V~12 + T cell subset responded normally to the superantigen. This V~-specific anergy, which was also observed in response to staphylococcal enterotoxin E (SEE), affected both CD4 + and CD8 + T cells and represented an intrinsic functional defect rather than a specific lack of response to bacterial superantigens since it was also observed after a stimulation with V//8 monoclonal antibodies. The V/~8 anergic T ceils did not express interlenkin 2 receptors (IL-2Rs) and failed to proliferate in response to exogenous IL-2 or IL-4, suggesting that this anergy was not a reversible process, at least by the use of these cytokines. The unresponsiveness of the V~8 T cell subset is frequent since it was found in 56% of the patients studied, and comparison of the clinical status of responder vs. anergic patients indicated that the only known common factor between them was HIV infection. In addition, it is noteworthy that the anergy of the V~8 subset may be a very early phenomenon since it was found in a patient at Centers for Disease Control stage I of the disease. These data provide evidence that a dominant superantigen may be involved in the course of HIV infection and that the contribution of HIV has to be considered.