Prolonged IL-2 receptor alpha/CD25 expression after T cell activation via the adhesion molecules CD2 and CD28. Demonstration of combined transcriptional and post-transcriptional regulation
| Autor: | C Cerdan, Y Martin, M Courcoul, H Brailly, C Mawas, F Birg, D Olive |
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| Rok vydání: | 1992 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 149:2255-2261 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The T cell adhesion molecule CD28 provides a costimulatory signal in combination with CD2 and CD3 mAb. CD28 regulates the expression of cytokines by T cells, not only IL-2, but also IL-1 alpha and CSF-1, usually synthesized by accessory cells. We have investigated the mechanisms through which CD28 modulates the expression of the IL-2R alpha chain. Whereas activation through CD2 or CD28 alone induced no or only low IL-2R alpha chain expression, activation through CD2 plus CD28 led to both a high and prolonged (greater than 14 days) cell surface and mRNA expression. In contrast, immobilized CD3 mAb-dependent activation induced a transient expression of the IL-2R alpha chain, which was neither further increased nor prolonged by CD28 costimulation. Upon CD2 plus CD28 stimulation, the half-lives of the two IL-2R alpha transcripts increased progressively between days 1 and 4, in contrast to each pathway alone. Whereas each activation pathway alone induced either no (CD2) or low (CD28) levels of IL-2R alpha gene transcription, the CD2 plus CD28 stimulation was associated with its increased transcription, which persisted at similar rates between 5 and 96 h post stimulation. The in vitro costimulation via the CD2 and CD28 molecules thus regulates the expression of the IL-2R alpha gene both at the transcriptional and post transcriptional levels. Our results therefore demonstrate a new immunoregulatory function of the CD28 molecule on IL-2R alpha expression, which, through its increased transcription rate and stabilization, could, together with high levels of cytokines secretion, be responsible for the prolonged T cell proliferation. |
| Databáze: | OpenAIRE |
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