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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4411-4419. Prepublished online as a Blood First Edition Paper on September 16, 2008; DOI 10.1182/blood-2007-03-080697. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-03-080697v1 112/12/4411    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wu, Z. Articles by Leonard, W. J. Search for Related Content PubMed PubMed Citation Articles by Wu, Z. Articles by Leonard, W. J. Related Collections Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS The IL-15 receptor chain cytoplasmic domain is critical for normal IL-15R function but is not required for trans-presentation Zheng Wu1, Hai-Hui Xue1, Jérôme Bernard1, Rong Zeng1, Dmitry Issakov2, Julie Bollenbacher-Reilley1, Igor M. Belyakov2, SangKon Oh2,3, Jay A. Berzofsky2, and Warren J. Leonard1 1 Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; 2 Vaccine Branch, National Cancer Institute, NIH, Bethesda, MD; and 3 Baylor Institute for Immunology Research, Baylor University Medical Center, Dallas, TX IL-15 is critical for natural killer (NK)–cell development and function and for memory CD8+ T-cell homeostasis. The IL-15 receptor consists of IL-15R, IL-2Rβ, and the common cytokine receptor chain (c). IL-15R is known to "trans-present" IL-15 to an IL-2Rβ/c heterodimeric receptor on responding cells to initiate signaling. To investigate the importance of the IL-15R cytoplasmic domain, we generated a chimeric receptor consisting of the extracellular domain of IL-15R and intracellular domain of IL-2R (IL-15Rext/IL-2Rint) and examined its function in 32D cells, in knock-in (KI) mice, and in adoptive-transfer experiments. The chimeric protein exhibited decreased cell-surface expression, and KI mice exhibited diminished NK, NKT, and CD8+ T-cell development and defects in T-cell functional responses. However, 32D cells expressing the chimeric receptor had less IL-15–induced proliferation than wild-type (WT) transfectants with similar levels of IL-15R expression, indicating a signaling role for the IL-15R cytoplasmic domain beyond its effect on expression, and demonstrating that the IL-2R and IL-15R cytoplasmic domains are functionally distinct. Interestingly, adoptive-transfer experiments indicated that the chimeric IL-15Rext/IL-2Rint receptor still supports trans-presentation. These experiments collectively indicate that IL-15R can act in cis in addition to acting in trans to present IL-15 to responding cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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