The programmed cell death theory of AIDS pathogenesis: implications, testable predictions, and confrontation with experimental findings

Abstract

The programmed cell death theory of acquired immunodeficiency syndrome (AIDS) pathogenesis postulates that most immunological and non-immunological defects in human immunodeficiency virus (HIV)-infected people are related to a single mechanism, the inappropriate expression in mature CD4+ T cells and other cell-populations such as neurons of an activation-induced physiological cell suicide program that plays an essential role during embryogenesis in the maturation of both the immune and the nervous systems. The theory is discussed in the context of a series of recent experimental findings indicating that mature T cells can, as immature thymocytes, undergo programmed cell death in response to T-cell receptor mobilization in various physiological and pathological circumstances including murine and human acquired immunodeficiency of retroviral origin. These findings provide new insights into the pathogenesis of AIDS and may have implications for the design of therapeutic strategies.