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 / ForeginForegin
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