AUTOIMMUNE T-CELL RESPONSE TO THE CD4 MOLECULE IN HIV-INFECTED PATIENTS

In a previous study, we demonstrated that by downregulating plasma mem brane CD4 and increasing its processing, human immunodeficiency (HIV)- 1-gp120 unveils hidden CD4 epitopes, inducing an in vitro anti-CD4-spe cific T-cell response. We report herein that this mechanism may potent ially have important implications in HIV immunopathogenesis, because i t could take part in the severe depletion of CD4(+) cells that charact erizes acquired immune deficiency syndrome (AIDS) and be related to di sease progression. Freshly isolated peripheral blood lymphocytes (PBMC ) from about 1/4 of a conspicuous cohort of HIV-infected patients resp onded to CD4 and this response was correlated with beta(2)-microglobul in levels, widely recognized as marker for progression of HIV infectio n. Moreover, we provide evidence that a CD4-specific T cell priming ca n occur in vivo, following a gp120 or anti-CD4 monoclonal antibody (mA b)-mediated CD4 molecule downregulation on antigen-presenting cells (A PC). To our knowledge, this is the first study indicating that an auto immune T-cell response is linked to HIV infection and that it could ha ve an important impact on the immunopathogenesis of this disease.