title: Activation-induced peripheral blood T cell apoptosis is Fas independent in HIV-infected individuals.
abstract: T cell apoptosis has been proposed as an important contributor to the functional defects and depletion of T cells in HIV-infected individuals. However, the mechanisms involved in this apoptosis have not been elucidated. We recently showed that peripheral blood T cells from HIV-infected individuals are especially susceptible to Fas antigen-induced apoptosis. In this study we examine the role of Fas, CTLA-4, tumor necrosis factor (TNF) receptors (TNFR) and CD30, receptors known to be involved in T cell activation-induced cell death (AICD), in the spontaneous and activation (anti-CD3)-induced apoptosis of peripheral blood T cells from asymptomatic HIV-infected individuals. We report here that spontaneous and activation-induced T cell apoptosis cannot be inhibited by reagents that block interactions of Fas, CTLA-4, p55 and p75 TNFR and CD30 with their respective ligands. We also show that IL-12, IFN-gamma, IL-4 and IL-10 cannot modify spontaneous, activation- and anti-Fas-induced apoptosis. Anti-Fas preferentially induced CD4+ T cell apoptosis whereas AICD induced apoptosis equally in CD4+ and CD8+ T cells. We conclude that T cell AICD in HIV infection is not mediated by Fas, thus indicating that Fas-induced and activation-induced T cell apoptosis are independent mechanisms of apoptosis which may play different roles in the pathogenesis of HIV infection.
authors.affiliation: Department of Genetics, Beckman Center B007, Stanford University School of Medicine, CA 94305, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Katsikis
authors.forename: M E
authors.initials: ME
authors.lastname: García-Ojeda
authors.forename: E S
authors.initials: ES
authors.lastname: Wunderlich
authors.forename: C A
authors.initials: CA
authors.lastname: Smith
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: N
authors.initials: N
authors.lastname: Kayagaki
authors.forename: M
authors.initials: M
authors.lastname: Alderson
authors.forename: L A
authors.initials: LA
authors.lastname: Herzenberg
authors.forename: L A
authors.initials: LA
authors.lastname: Herzenberg
mesh_terms: D000069594:Abatacept; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D018796:Immunoconjugates; D066298:In Vitro Techniques; D017730:Ki-1 Antigen / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D018796:Immunoconjugates; D017730:Ki-1 Antigen; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D000069594:Abatacept