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.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Takaku S,Nakagawa Y,Owaki A,Shimizu M,Takahashi M,Takahashi H

doi

10.1016/j.cellimm.2012.12.008

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

138-47

issue

2

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(13)00005-1

journal_volume

280

pub_type

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