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This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kishimoto, H. Articles by Abe, R. PubMed Articles by Kishimoto, H. Articles by Abe, R.

Induction of pro-apoptotic signals via the CD28 in the thymus

Research Institute for Biological Sciences, Tokyo University of Science, Noda-City, Japan

ABSTRACT

Along with TCR signal, costimulatory signal given by CD28 plays a key roles in deciding the fate of T cells. Decision of death or survival of T cells by CD28 signal depends on the development stages of T cells. TCR+CD28 signals induce activation, proliferation and production of various cytokines in mature peripheral T cells whereas apoptosis is induced in CD4⁺8⁺ and CD24⁺CD4⁺8^– thymocytes by TCR+CD28 signals. PI3K and Grb2/Gads have been shown to be recruited the YMNM motif in CD28 cytoplasmic portion, and LCK and ITK could associate with two PXXP motifs. To elucidate pro-apoptotic signals induced by CD28, we established transgenic (Tg) mice expressing CD28 that have various mutations in CD28 cytoplasmic portion, and investigated susceptibility of CD4⁺8⁺ and CD24⁺CD4⁺8^– thymocytes from those mutant CD28 mice to apoptosis induced by TCR+CD28 ligation. When immature and semi-mature thymocytes form various CD28 mutant Tg mouse lines were stimulated with TCR+CD28 mAbs, thymocytes from the YF line and the ncPA line of CD28 mutant Tg mice showed complete abrogation of pro-apoptotic function by CD28 signaling. The YF Tg line has no ability to recruit PI3K and Grb2/Gads, and the ncPA Tg line that is not designed to associate with neither LCK nor ITK. These results indicated that phosphorylation of the tyrosine residue in YMNM motif is indispensable for induction of pro-apoptotic function in developing thymocytes by CD28.

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kishimoto, H. Articles by Abe, R. PubMed Articles by Kishimoto, H. Articles by Abe, R.