Does HIV cause depletion of CD4+ T cells in vivo by the induction of apoptosis?

Abstract

SummaryThe central pathogenic feature of AIDS is the dramatic loss of CD4+ lymphocytes. Despite more than a decade of intense research, the exact mechanism by which HIV causes this is still not understood. A major model for T cell depletion, proposed originally by Ameison and Capron in a report published in 1991, is that HIV sensitizes CD4+ T cells for activation-induced apoptosis. The apoptotic model of T cell depletion is discussed, and experiments that address the questions of whether apoptosis is restricted to infected cells or 'bystander' T cells, and whether T cell apoptosis requires participation of separate HIV-infected haematopoietic cell populations, are reviewed.

CD4-Lck Through TCR and in the Absence of Vav Exchange Factor Induces Bax Increase and Mitochondrial Damage

“…However, the large amount of evidence demonstrating that CD4 regulates apoptosis has been obtained after separate ligation of CD4 and TCR (11, 40 -43). This has been a good approach to analyze the effects of CD4 antagonist ligands such as anti-CD4 Abs (44) or HIV gp120 (45,46). Indeed, this approach has provided useful information to control autoimmune diseases and organ graft rejection and to explain CD4 ϩ T cell deletion in AIDS.…”

Death of CD4+T-Cell Lines Caused by Human Immunodeficiency Virus Type 1 Does Not Depend on Caspases or Apoptosis

“…Apoptosis has been implicated in the cytopathicity of several human and animal viruses, including retroviruses such as HIV-1 (7,9,26). Apoptosis is defined as an active physiological process of cellular self-destruction, distinguished by a specific series of morphological and biochemical changes that stem from the activation of the caspase family of cysteine proteases (45).…”

“…Evidence has suggested that apoptosis could play a role in both direct killing of infected CD4 ϩ T cells, as well as in the death of uninfected bystander CD4 ϩ T cells (26). The first reports documenting HIV-1-induced apoptosis demonstrated fragmentation of cellular DNA among infected T-cell cultures (32,55).…”

Partial Activation and Induction of Apoptosis in CD4+and CD8+T Lymphocytes by Conformationally Authentic Noninfectious Human Immunodeficiency Virus Type 1

“…These include the direct lysis of CD4 ϩ T cells from virus infection (26), syncytium formation (44,77), superantigen-mediated deletion (34,66), macrophage-dependent killing (8), and CD8 ϩ T-cell-dependent killing (76). Apoptosis has also been implicated as a mechanism for the death of both HIV-infected and uninfected cells (30,35). However, differences between experimental systems and the direct cytopathic effects of replicating virus have complicated interpretation of these studies, and it is still largely unresolved as to whether noninfectious HIV virions can induce apoptosis and cell death.…”