Priming of human CD4+ antigen-specific T cells to undergo apoptosis by HIV-infected monocytes. A two-step mechanism involving the gp120 molecule.
The study of the pathology of HIV-1 infection in chimpanzees supports the idea of the crucial role of HIV-infected monocytes in the pathogenesis of AIDS, although viral mechanisms that lead to T cell dysfunction and deletion during HIV infection are still unclear. We show here that HIV-1-infected antigen-presenting monocytes (APCs) are able to prime in vitro non-HIV-infected antigen-specific CD4+ T cell lines or peripheral blood CD4+ T cells to undergo apoptosis after antigen-specific restimulation. The priming of T cells for apoptosis occurs in the absence of HIV replication in the T cells. Priming for apoptosis required two concomitant signals present on the same APC, an antigenic stimulus and a second signal provided by the HIV gp120 protein as demonstrated by the use as APCs of EBV-LCLs infected with different recombinant deleted proviruses or transfected with different HIV proteins. These results provide a mechanism for the priming for apoptosis of T cells in HIV-infected patients, implicating a role for HIV-infected APCs in the induction of T cell dysfunction and depletion in AIDS.
Cottrez
F
F
Unité mixte Institut National de la Santé et de la Recherche Médicale U167-CNRS 624, Institut Pasteur, Lille, France.
Manca
F
F
Dalgleish
A G
AG
Arenzana-Seisdedos
F
F
Capron
A
A
Groux
H
H
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015752:Genes, env; D015756:Genes, tat; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology* / Q000821:virology*; D011533:Proviruses / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic
D015699:HIV Envelope Protein gp120