IWASAKI Masayuki    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	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.
Journal	Formal name：European journal of immunology Abbreviation：Eur J Immunol ISSN code：00142980/00142980
Domestic / Foregin	Foregin
Volume, Issue, Page	31(5),pp.1456-64
Author and coauthor	Park W R, Park C S, Tomura M, Ahn H J, Nakahira Y, Iwasaki M, Gao P, Abe R, Hamaoka T, Fujiwara H
Publication date	2001/05
Summary	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-y 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.
DOI	10.1002/1521-4141(200105)31:5<1456::AID-IMMU1456>3.0.CO;2-A
PMID	11465102