Cellular distribution and costimulatory function of rat CD28. Regulated expression during thymocyte maturation and induction of cyclosporin A sensitivity of costimulated T cell responses by phorbol ester.
CD28 has been identified in man and mouse as a potent costimulatory receptor on T cells. We have generated a mAb, called JJ319, to rat CD28 and show that it is expressed on virtually all peripheral rat alpha beta and on most gamma delta T cells, and on about half of NK cells. In contrast to the mouse but as in humans, most immature CD4+8+TCRlow thymocytes express little or no CD28, whereas CD28 expression is high on TCRintermediate and TCRhigh cells. mAb JJ319 very effectively costimulates T cell proliferation and IL-2 secretion by resting rat T cells. In contrast to results obtained in mice and humans, phorbol ester did not synergize in T cell activation with CD28-specific mAb but even induced sensitivity to cyclosporin A in T cell cultures that were optimally costimulated by mAbs to the TCR and to CD28. This result points to a novel effect of protein kinase activation by phorbol ester on signal transduction by TCR plus CD28 costimulation which only becomes apparent if, as in the rat, the TCR-mediated signal cannot be replaced by phorbol ester.
Tacke
M
M
Institute for Virology and Immunobiology, University of Würzburg, Germany.
Clark
G J
GJ
Dallman
M J
MJ
Hünig
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018106:CD28 Antigens / Q000032:analysis* / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D018076:DNA, Complementary; D016572:Cyclosporine; D013755:Tetradecanoylphorbol Acetate