International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 120 - IL-15Ra IS A NEGATIVE REGULATOR OF THE ACTIVATION OF CD4+ T CELLS AND AUTOIMMUNITY

Lee JM, Hou MS, Chung CY, Chiang WW, Yang ST, Liou YH, Liao NS

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

Although IL-15 is known to be a T cell growth factor, the function in T cells of IL‑15Ra, its high affinity receptor, remains unclear. We found that IL‑15Ra -/- CD4+ T cells hyperproliferated in response to TCR stimulation, in vitro and in vivo, and displayed a lower TCR activation threshold than wild type (wt) CD4+ T cells. TCR-induced activation of Zap70 and of the PLC-g1-Ca ++-NFATp, Ras-ERK-c-Fos, and Rac-JNK-c-Jun pathways were all augmented in IL-15Ra -/- CD4+ T cells.  This in turn led to earlier IL-2Ra induction, higher IL-2 production and hyperproliferation. Exogenous IL-15 reduced levels of TCR-induced transcription factors, IL-2 and IL-2Ra and division in wt CD4+ T cells. In addition, the majority of aged female IL-15Ra -/- mice developed lupus-like symptoms. These results reveal IL-15Ra to be a negative regulator for CD4+ T cell activation and autoimmunity, and demonstrate a novel layer of regulation of TCR signaling by a cytokine system.

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