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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3704-3712. Prepublished online as a Blood First Edition Paper on August 8, 2008; DOI 10.1182/blood-2008-06-160945. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-160945v1 112/9/3704    most recent Alert me when this article is cited Alert me if a correction is posted 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rubinstein, M. P Articles by Goldrath, A. W. Search for Related Content PubMed PubMed Citation Articles by Rubinstein, M. P Articles by Goldrath, A. W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 3, 2008 Accepted July 25, 2008 IL-7 and IL-15 differentially regulate CD8+ T cell subsets during contraction of the immune response Mark P Rubinstein, Nicholas A Lind, Jared F Purton, Pauline Filippou, J Adam Best, Patrick A McGhee, Charles D Surh, and Ananda W. Goldrath* Biological Sciences, University of California, San Diego, La Jolla, CA, United States Immunology, The Scripps Research Institute, La Jolla, CA, United States * Corresponding author; email: agoldrath{at}ucsd.edu. While it is known that interleukin (IL)-7 and IL-15 influence the survival and turnover of CD8+ T cells, less is known about how these cytokines affect different subsets of CD8+ T cells during the course of the immune response. We find that IL-7 and IL-15 differentially regulate CD8+ T cell subsets defined by KLRG1 and CD127 expression during the contraction phase of the immune response. The provision of IL-15, or the related cytokine IL-2, during contraction, led to the preferential accumulation of KLRG1hiCD127lo CD8+ T cells, while provision of IL-7 instead favored the accumulation of KLRG1loCD127hi. Interestingly, while both IL-7 and IL-15 induced proliferation of KLRG1lo CD8+ T cells, KLRG1hi cells exhibited an extraordinarily high level of resistance to cytokine-driven proliferation in vivo despite their dramatic accumulation upon IL-15 administration. These results suggest that IL-15 and IL-2 greatly improve the survival of KLRG1hi CD8+ T cells, which are usually destined to perish during contraction, in the absence of proliferation. As the availability of IL-15 and IL-2 is enhanced during periods of extended inflammation, our results suggest a mechanism where a population of cytokine-dependent KLRG1hi CD8+ T cells is temporarily retained for improved immunity. Consideration of these findings may aid in the development of therapies for augmenting T cell-directed immunotherapeutic strategies against infectious disease and cancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. P. Cheung, E. Yang, and A. W. Goldrath Memory-Like CD8+ T Cells Generated during Homeostatic Proliferation Defer to Antigen-Experienced Memory Cells J. Immunol., September 1, 2009; 183(5): 3364 - 3372. [Abstract] [Full Text] [PDF]

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