SELECTIVE ANERGY OF V-BETA-8(-CELLS IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALS() T)

We have analyzed the V beta usage by CD4(+) and CD8(+) T cells from hu man immunodeficiency virus (HIV)-infected individuals in response to a n in vitro stimulation with the superantigenic erythrogenic toxin A (E TA) of Streptococcus pyogenes. ETA amplifies specifically CD4(+) and C D8 + T cells from control donors expressing the V beta 8 and the V bet a 12 elements. When peripheral T cells from asymptomatic HIV-infected individuals were stimulated with ETA, there was a complete lack of act ivation of the V beta 8(+) T cell subset, whereas the V beta 12(+) T c ell subset responded normally to the superantigen. This V beta-specifi c anergy, which was also observed in response to staphylococcal entero toxin E (SEE), affected both CD4(+) and CD8(+) T cells and represented an intrinsic functional defect rather than a specific lack of respons e to bacterial superantigens since it was also observed after a stimul ation with V beta 8 monoclonal antibodies. The V beta 8 anergic T cell s did not express interleukin 2 receptors (IL-2Rs) and failed to proli ferate in response to exogenous IL-2 or IL-4, suggesting that this ane rgy was not a reversible process, at least by the use of these cytokin es. The unresponsiveness of the V beta 8 T cell subset is frequent sin ce it was found in 56% of the patients studied, and comparison of the clinical status of responder vs. anergic patients indicated that the o nly known common factor between them was HIV infection. In addition, i t is noteworthy that the anergy of the V beta 8 subset may be a very e arly phenomenon since it was found in a patient at Centers for Disease Control stage I of the disease. These data provide evidence that a do minant superantigen may be involved in the course of HIV infection and that the contribution of HIV has to be considered.