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CD28 costimulation is required not only to induce IL‐12 receptor but also to render Janus kinases / STAT4 responsive to IL‐12 stimulation in TCR‐triggered T cells
Author(s) -
Park WoongRyeon,
Park CheungSeog,
Tomura Michio,
Ahn HyunJong,
Nakahira Yasukiyo,
Iwasaki Masayuki,
Gao Ping,
Abe Ryo,
Hamaoka Toshiyuki,
Fujiwara Hiromi
Publication year - 2001
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/1521-4141(200105)31:5<1456::aid-immu1456>3.0.co;2-a
Subject(s) - cd28 , biology , stat4 , microbiology and biotechnology , stimulation , t cell receptor , t cell , cd40 , phosphorylation , il 2 receptor , cd3 , immunology , cytotoxic t cell , stat , endocrinology , stat3 , antigen , cd8 , immune system , in vitro , biochemistry
Abstract The activation of resting T cells for the acquisition of various functions depends on whether CD28 costimulatory signals are provided upon T cell receptor stimulation. Here, we investigated how CD28 costimulation functions to allow TCR‐triggered resting T cells to acquire IL‐12 responsiveness. When T cells are stimulated with low doses of anti‐CD3 mAb, CD28 costimulation was required for the optimal levels of IL‐12 receptor (IL‐12R) expression. However, stimulation of T cells with high doses of anti‐CD3 alone induced comparable levels of IL‐12R expression to those induced upon CD28 costimulation. Nevertheless, there was a substantial difference in IL‐12 responsiveness between these two groups of T cells: compared to anti‐CD28‐costimulated T cells, T cells that were not costimulated with anti‐CD28 exhibited decreased levels of Janus kinases (JAK) JAK2 / TYK2 and STAT4 phosphorylation and IFN‐γ production following IL‐12 stimulation. Importantly, STAT6 phosphorylation following IL‐4 stimulation was not decreased in anti‐CD28‐uncostimulated T cells. These resutls indicate that CD28 costimulation not only contributes to up‐regulating IL‐12R expression but is also required to render JAKs / STAT4 responsive to IL‐12 stimulation.