title: Induction of apoptosis-resistant and TGF-β-insensitive murine CD8(+) cytotoxic T lymphocytes specific for HIV-1 gp160.
abstract: Although TGF-β and IL-6 would turn CD8(+) T cells to differentiate into non-cytotoxic state, these treated cells were converted to cytolytic phenotypes after re-exposure to their antigenic epitope in vitro. Here, using spleen cells from TCR transgenic mice expressing TCRαβ genes of clone RT1 recognizing an epitope peptide (P18-I10: RGPGRAFVTI) of HIV-1 gp160, we generated CD8(+) cytotoxic T lymphocytes (CTLs) activated by re-exposure to P18-I10 after primarily cultured with TGF-β and IL-6 in vitro to examine their effector function. The CTLs, having strong cytotoxic activity in vitro, were not only resistant to Fas-FasL mediated apoptosis, but also insensitive to the suppression of their cytotoxicity by re-exposure to TGF-β in vitro. Moreover, adoptive transfer experiments indicated that the CTLs are capable of eliminating recombinant vaccinia virus expressing HIV-1 gp160 in vivo. Taken together, our data suggest that TGF-β and IL-6 may play pivotal roles in inducing apoptosis-resistant and TGF-β-insensitive CTLs in vitro.
authors: Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, Japan. salsa@nms.ac.jp
authors: Shun
authors: S
authors: Takaku
authors: Yohko
authors: Y
authors: Nakagawa
authors: Atsuko
authors: A
authors: Owaki
authors: Masumi
authors: M
authors: Shimizu
authors: Megumi
authors: M
authors: Takahashi
authors: Hidemi
authors: H
authors: Takahashi
mesh_terms: D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015850:Interleukin-6 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D019014:fas Receptor / Q000502:physiology
chemical_list: D000939:Epitopes; D019302:HIV Envelope Protein gp160; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D019014:fas Receptor; C514797:gp160 protein, Human immunodeficiency virus 1