[Programmed death (apoptosis) of T CD4 lymphocytes and AIDS pathogenesis].
A major characteristic of human immunodeficiency virus (HIV) infection is progressive decline in T CD4+ lymphocytes. Ten years after infection, on average, this cell subpopulation disappears and AIDS develops. In the asymptotic phase T CD4+ lymphocytes no longer respond, in vitro or in vivo, to certain memory antigens constrained by the class II histocompatibility complex, or in vitro to polyclonal activators like pokeweed mitogen. They retain, however, some proliferative response activity and constitute only a small proportion of the T CD4+ population. Indirect mechanisms of depletion are therefore sought. We have proposed a hypothesis for a single mechanism: a programmed death process, apoptosis, reactivated in mature T CD4+ lymphocytes of seropositives. Unlike necrosis, apoptosis has a role in embryogenesis, in the adult in certain cell populations and, in immature thymocytes, in T lymphocyte selection and establishment of self-tolerance. T CD4+ lymphocytes of infected subjects lose their ability to proliferate in vitro, as they undergo a form of suicide in response to certain stimuli. In vivo T CD4+ cell activation induced by various infectious agents, including HIV, progressively reduces the subpopulation, independently of the virus' cytopathogenic effect. Tests were performed that explored the T CD4+ lymphocyte response to super-antigens, which mimic and amplify the effect of memory antigens by way of CMH II molecules of Ag-presenting cells and certain nu beta chains of the alpha beta receptor for the Ag which are expressed by a third of human mature T CD4+ lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Ameisen
J C
JC
Centre d'Immunologie et de Biologie parasitaire, Unité mixte I.N.S.E.R.M. U. 167-C.N.R.S. 624, Institut Pasteur, Lille, France.
Groux
H
H
Capron
A
A
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans
Mort programmée (apoptose) des lymphocytes T CD4+ et pathogénie du SIDA.