HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, J.-M. Articles by Liao, N.-S. Search for Related Content PubMed PubMed Citation Articles by Lee, J.-M. Articles by Liao, N.-S.

IL-15R Is a Negative Regulator of TCR-Activated Proliferation in CD4⁺ T Cells¹

Jan-Mou Lee^*,, Chen-Yen Chung, Wei-Wei Chiang, Yae-Huei Liou, Chian-Feng Chen^*, and Nan-Shih Liao^2,*,

^* Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; and 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-15R, its high affinity receptor, remains unclear. We found that murine IL-15R^–/– CD4⁺ T cells hyperproliferated in response to TCR stimulation, in vitro and in vivo, and displayed a lower TCR activation threshold than wild-type CD4⁺ T cells. TCR-induced activation of Zap70 and of the phospholipase C-1-NFATp, Ras-ERK-c-Fos, and Rac-JNK-c-Jun pathways was all augmented in IL-15R^–/– CD4⁺ T cells. This in turn led to earlier IL-2R induction and higher IL-2 production, which most likely contribute to the hyperproliferation of IL-15R^–/– CD4⁺ T cells. Exogenous IL-15 reduced levels of TCR-activated signals, transcription factors, IL-2, and IL-2R, and division in wild-type CD4⁺ T cells. These results reveal IL-15R to be a negative regulator for CD4⁺ T cell activation and demonstrate a novel layer of regulation of TCR signaling by a cytokine system.

This article has been cited by other articles:

				L. Baranda, H. de la Fuente, E. Layseca-Espinosa, D. Portales-Perez, P. Nino-Moreno, G. Valencia-Pacheco, C. Abud-Mendoza, J. Alcocer-Varela, and R. Gonzalez-Amaro IL-15 and IL-15R in leucocytes from patients with systemic lupus erythematosus Rheumatology, December 1, 2005; 44(12): 1507 - 1513. [Abstract] [Full Text] [PDF]