PATHOGENIC DISORDERS INVOLVED IN IMMUNOSUPPRESSION AND T-CELL DEPLETION CHARACTERIZING AIDS

Four cardinal immune disorders interacting with each other may promote the progressive T cell depletion and immunosuppression characterizing AIDS. Immune activation of HIV-1 infected T4 cells leads to virus rel ease and premature cell death. Both virus release with its resulting v iral load and dead cells are the source of gp120 stimulus. Anergy of n on-infected CD4 cells, resulting in cytokine dysregulation may be prom oted by impairing the CD4-MHC interaction during CD4 cell activation e ither directly through the SLWDQ pentapeptide identity with the CD4 mo lecule and the CD4 binding region or through a gp120-induced autoimmun e reaction to CD4. Overproduction of IFN alpha, the known antiprolifer ative and cytolytic cytokine may promote in a paracrine manner to neig hbouring cells the immunosuppression generated by the lack of IL2 secr etion following CD4 cell anergy. Apoptosis of activated non infected T cells could be induced by effector components of the autoimmune react ion (CTL, Lymphotoxins or Abs?) directed towards the 2 consensus gp120 sequence identity/similarity (INCTR and FYCNST) shared with the APO/F as molecule. These two sequences are known as immunodominant sites of the gp120. Furthermore, IFN alpha overproduction may also render circu lating memory T cells competent to apoptosis by upregulating the casca de of metabolic events leading to programmed cell death.