Programmed Death of T Cells in the Course of HIV Infection

Abstract

Infection with the human immunodeficiency virus (HIV) is characterized by an asymptomatic phase of variable length and a decline in CD4+ T-cell numbers, eventually leading to the acquired immune deficiency syndrome (AIDS). Importantly, even before CD4+ T-cell numbers start to decline, functional abnormalities of T cells can be demonstrated in asymptomatically infected individuals. Both CD4+ and CD8+ T-cell function such as IL-2 production and proliferation in response to recall antigens and CD3 antibodies is affected (Shearer et al.1984; Miedema et al.1988; Schellekens et al.1990). One of the enigmas of AIDS pathogenesis is the mechanism by which HIV is capable of perturbing immune functions in a stage of infection where the number of infected cells is low (Schnittman et al.1989). In the past few years, several possible mechanisms have been investigated, including specific loss of memory cells, induction of anergy by antigen presenting cell dysfunction or dysregulation of the Thl/Th2 cytokine balance (reviewed in (Miedema et al.1994)). Following the hypothesis by Ameisen et al (Ameisen et al.1991), who proposed apoptosis as a mechanism for CD4+ T-cell depletion and loss of cellular immune function, several groups, including our group, have investigated PCD of (CD4+) T cells as a possible cause of T-cell dysfunction and CD4+ T-cell depletion in HIV-infected individuals.