CD28 costimulation up-regulates long-term IL-2R beta expression in human T cells through combined transcriptional and post-transcriptional regulation.
Costimulatory molecules such as CD28 are required for induction of T cell clonal expansion and for prevention of T cell unresponsiveness. In combination with either CD3 or CD2 triggering, CD28 was shown to enhance T cell proliferation, cytolytic activity, production of cytokines and especially of IL-2, and expression of the IL-2R alpha-chain (IL-2R alpha). We and others have demonstrated that the costimulatory effect of CD28 on both IL-2 and IL-2R alpha expression results from a coordinated transcriptional activation of their genes and transcript stabilization. We show here that the CD28 stimulation, together with CD2, leads to a prolonged up-regulation of the constitutive expression of the IL-2R beta-chain in human peripheral T cells. As for IL-2R alpha, the increase in IL-2R beta gene expression seems to result from both transcriptional activation and transcript stabilization. In addition, IL-2 differentially regulates its own receptors, as only expression of IL-2R alpha, but not of IL-2R beta, is largely inhibited, at both the mRNA and protein levels, by blocking IL-2R mAbs. We propose that the long lasting T cell proliferation mediated by the CD2 and CD28 costimulation is mainly the consequence of the high and prolonged expression of both the IL-2R alpha- and beta-chains.
Cerdan
C
C
Unit 119, National Institute of Health and Medical Research, Marseilles, France.
Martin
Y
Y
Courcoul
M
M
Mawas
C
C
Birg
F
F
Olive
D
D
D015152:Blotting, Northern; D018801:CD2 Antigens / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000302:isolation & purification; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
D018801:CD2 Antigens; D018106:CD28 Antigens; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2