Anergy and apoptosis in CD8+ T cells from HIV-infected persons.
CD8+T cells from HIV-infected persons increase early in infection, display increased levels of activation Ags, and abnormal MHC-restricted, HIV-specific and nonspecific cytotoxicity abilities. Paradoxically, these cells are also unresponsive to T cell signaling in vitro and have decreased in vitro cloning potential. HIV-specific CTL precursors also are lost late in infection. A quantitative Southern blotting technique showed that CD8+ T cells from asymptomatic, HIV-infected persons have increased DNA fragmentation after overnight incubation. DNA fragmentation was reduced by an endonuclease inhibitor but not by cycloheximide, suggesting that a pre-apoptotic state exists in vivo. Partial inhibition of DNA fragmentation also could be induced by IL-2 addition. No consistent difference in fragmentation was observed among CD8+ subpopulations from HIV-infected individuals, although only CD8+ T cells that did not express activation Ags (DR-, CD28+, CD57- phenotype) showed reduced fragmentation when incubated in IL-2. A dramatic increase in CD8+, CD28- cells was observed in asymptomatic HIV-infected people. A subset of CD8+, CD28- cells in both controls and HIV-infected people do not proliferate to T cell signals, and these cells from controls demonstrate increased DNA fragmentation in vitro after 3 days of incubation, regardless of stimulation conditions. This suggests that the cells are end-stage cells. Taken together, the data suggest an increase in anergic or apoptotic CD8+ T cells in HIV-infected persons. Eventual depletion of HIV-specific CD8+ T cells may occur through a process of proliferation, anergy induction, and apoptosis.
Lewis
D E
DE
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.
Tang
D S
DS
Adu-Oppong
A
A
Schober
W
W
Rodgers
J R
JR
D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018959:CD57 Antigens; D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018959:CD57 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2