Induction of apoptosis-resistant and TGF-β-insensitive murine CD8+ cytotoxic T lymphocytes specific for HIV-1 gp160

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.