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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2789-2795. Prepublished online as a Blood First Edition Paper on June 20, 2006; DOI 10.1182/blood-2006-05-025676. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-025676v1 108/8/2789    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lucas, P. J. Articles by Gress, R. E. Search for Related Content PubMed PubMed Citation Articles by Lucas, P. J. Articles by Gress, R. E. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Dysregulation of IL-15-mediated T-cell homeostasis in TGF- dominant-negative receptor transgenic mice Philip J. Lucas, Seong-Jin Kim, Crystal L. Mackall, William G. Telford, Yu-Waye Chu, Frances T. Hakim, and Ronald E. Gress From the Experimental Transplantation and Immunology Branch, the Laboratory of Cell Regulation and Carcinogenesis, and the Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. T-cell subpopulations, defined by their expression of CD4, CD8, naive, and memory cell-surface markers, occupy distinct homeostatic compartments that are regulated primarily by cytokines. CD8+ memory T cells, as defined by CD44hi surface expression, are dependent on IL-15 as a positive regulator of their homeostatic maintenance. Manipulation of IL-15 signaling through gene aberration, overexpression, or receptor alterations has been shown to dramatically affect T-cell homeostasis, with overexpression leading to fatal leukemia. Here we show that TGF- is the critical negative regulator of murine CD8+ memory T-cell homeostasis with direct opposition to the positive effects of IL-15. This negative regulation is mediated, at least in part, by the ability of TGF- to modulate expression of the -chain of the IL-15 receptor, thus establishing a central axis between these 2 cytokines for homeostatic control of CD8+ memory T-cell populations. These data establish TGF- as a critical and dominant tumor-suppressor pathway opposing IL-15-mediated CD8+ T-cell expansion and potential malignant transformation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-s. Wang, G.-q. Wang, Y.-j. Wen, L. Wang, X.-c. Chen, P. Chen, B. Kan, J. Li, C. Huang, Y. Lu, et al. Immunity against Tumor Angiogenesis Induced by a Fusion Vaccine with Murine {beta}-Defensin 2 and mFlk-1 Clin. Cancer Res., November 15, 2007; 13(22): 6779 - 6787. [Abstract] [Full Text] [PDF] J. S. Miller, D. J. Weisdorf, L. J. Burns, A. Slungaard, J. E. Wagner, M. R. Verneris, S. Cooley, R. Wangen, S. K. Fautsch, R. Nicklow, et al. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone Blood, October 1, 2007; 110(7): 2761 - 2763. [Abstract] [Full Text] [PDF]

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