SELECTIVE CD4(-CELL DELETION AFTER SPECIFIC ACTIVATION IN HIV-INFECTED INDIVIDUALS - PROTECTION BY ANTI-CD28 MONOCLONAL-ANTIBODIES() T)

AIDS is characterized by a progressive decline in the number of CD4(+) T cells. This is preceded by an early selective defect in the prolife ration of these cells to recall antigens [1-3], pokeweed mitogen (PWM) [4-6] and to superantigens (SAg) [4,7]. In contrast, the proliferativ e response to phytohaemagglutinin (PHA) remains intact [1,2,5]. We and others have shown that the proliferative defect in response to some s timuli was in fact due to the induction of cell death [4.7]. The activ ation-induced cell death mechanism that explains the proliferative def ects observed in vitro might also account for the progressive in vivo deletion of CD4(+) T cells. Indeed, studies performed on different mod els of primates have shown that induction of cell death in CD4(+) T ce lls was detected only when T cells were isolated from animals infected with a type of retrovirus that induces an AIDS-like disease [8]. This correlation prompted us to analyse further the mechanism of HIV-induc ed activation cell death to determine the specificity and rate of indu ction of cell death. T cells from HIV-infected individuals were activa ted with superantigens and the VP T cell receptor (TCR) expression ana lysed. Data presented here show that cell death is restricted to activ ated CD4(+) T cells, and does not affect bystander cells. More importa ntly, addition of anti-CD28 MoAb specifically inhibited the induction of apoptosis, raising possibilities for therapy.