Infection and apoptotic cell death of CD4+ T cells during an immune response to HIV-1-pulsed dendritic cells.
Interacting dendritic cells and helper CD4+ lymphocytes form a microenvironment that is permissive for HIV-1 replication. The virus need only be pulsed initially onto the dendritic cells, which then transfer HIV-1 to the lymphocytes that are responding to presented antigens or superantigens. We have pursued underlying mechanisms in this system, because it provides a model for the infection of antigen-reactive, primary T cells. Pulsing the T cells with HIV-1 results in much less of a subsequent infection than does pulsing the dendritic cells. The latter pulse occurs effectively in the presence of AZT. Direct examination of the interacting dendritic cells and T cells reveals extensive production of p24 by many of the lymphocytes, including syncytia. The majority of the responding T cells die during the coculture. Apoptosis accounts for much of this death as revealed by in situ nick translation assays for DNA endonucleolysis, and hypodiploid profiles on staining with DNA-binding dyes. Therefore the microenvironment that is generated between antigen-presenting dendritic cells and T cells reveals the cytopathic potential of HIV-1, because there is such extensive and rapid death by apoptosis of antigen-reactive T cells.
Cameron
P U
PU
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
Pope
M
M
Gezelter
S
S
Steinman
R M
RM
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004352:Drug Resistance, Microbial; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D015215:Zidovudine / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016655:HIV Core Protein p24; D015215:Zidovudine; D017493:Leukocyte Common Antigens