AIDS AND THE DEATH RECEPTORS

Activation-induced cell death (AICD) of T cells involves the CD95 rece ptor/ligand system. T cell activation through the T cell receptor resu lts in expression of the CD95 ligand (CD95L) that acts on CD95(+) cell s by direct binding and in a paracrine or autocrine Fashion. In AIDS, upregulation of CD95L in T cells is accelerated by two viral gene prod ucts, HIV-1 Tat and gp120. The CD95 signaling pathway is, therefore, l ikely to represent an important road to cell death of the CD4(+) T cel ls in AIDS. Recently, the early events in the CD95 signaling pathway h ave been identified. A key role hereby plays a receptor-interacting me mber of the interleukin 1 beta-converting enzymes (ICE), FLICE, that c ould be a target for therapeutic intervention. In addition to CD95, th e role of other members of the TNF receptor superfamily in AIDS is dis cussed.