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Role of T‐bet, the master regulator of Th1 cells, in the cytotoxicity of murine CD4 + T cells
Author(s) -
Eshima Koji,
Misawa Kana,
Ohashi Chihiro,
Iwabuchi Kazuya
Publication year - 2018
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/1348-0421.12586
Subject(s) - cytotoxicity , biology , regulator , microbiology and biotechnology , cytotoxic t cell , biochemistry , in vitro , gene
Although CD4 + T cells are generally regarded as helper T cells, some activated CD4 + T cells have cytotoxic properties. Given that CD4 + cytotoxic T lymphocytes (CTLs) often secrete IFN‐γ, CTL activity among CD4 + T cells may be attributable to Th1 cells, where a T‐box family molecule, T‐bet serves as the “master regulator”. However, although the essential contribution of T‐bet to expression of IFN‐γ has been well‐documented, it remains unclear whether T‐bet is involved in CD4 + T cell‐mediated cytotoxicity. In this study, to investigate the ability of T‐bet to confer cytolytic activity on CD4 + T cells, the T‐bet gene ( Tbx21 ) was introduced into non‐cytocidal CD4 + T cell lines and their cytolytic function analyzed. Up‐regulation of FasL (CD178), which provided the transfectant with cytotoxicity, was observed in Tbx21 transfected CD4 + T cells but not in untransfected parental cells. In one cell line, T‐bet transduction also induced perforin gene ( Prf1 ) expression and Tbx21 transfectants efficiently killed Fas − target cells. Although T‐bet was found to repress up‐regulation of CD40L (CD154), which controls FasL‐mediated cytolysis, the extent of CD40L up‐regulation on in vitro ‐differentiated Th1 cells was similar to that on Th2 cells, suggesting the existence of a compensatory mechanism. These results collectively indicate that T‐bet may be involved in the expression of genes, such as FasL and Prf1 , which confer cytotoxicity on Th1 cells.