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Blood, 26 March 2009, Vol. 113, No. 13, pp. 2934-2944. Prepublished online as a Blood First Edition Paper on January 9, 2009; DOI 10.1182/blood-2008-09-181164. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-09-181164v1 113/13/2934    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 Collazo, M. M. Articles by Kerr, W. G. Search for Related Content PubMed PubMed Citation Articles by Collazo, M. M. Articles by Kerr, W. G. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY SHIP limits immunoregulatory capacity in the T-cell compartment Michelle M. Collazo1, Daniela Wood1, Kim H. T. Paraiso1, Erin Lund2, Robert W. Engelman2, Cam-Tien Le3, Diana Stauch3, Katja Kotsch3,*, and William G. Kerr1,* Departments of 1 Immunology and 2 Pathology & Cell Biology, Moffitt Comprehensive Cancer Center and Research Institute, Tampa, FL; and 3 Universität Charité, Berlin, Germany Regulatory T cells (Tregs) play a pivotal role in preventing autoimmunity, graft-versus-host disease (GVHD), and organ graft rejection. We previously showed that either germline or induced SH2 domain–containing inositol 5-phosphatase (SHIP) deficiency in the host abrogates GVHD. Here we show that SHIP deficiency promotes an increase of CD4+CD25+FoxP3+ Tregs and CD4+CD25–FoxP3+"naive" T cells in the periphery that display increased CD103, glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR), OX40, and FcRII/III expression. SHIP deficiency does not compromise Treg function because SHIP-deficient CD3+CD4+CD25+ Tregs are as suppressive as wild-type (WT) CD3+CD4+CD25+ Treg. Interestingly, like conventional Tregs, SHIP–/– CD4+CD25– T cells are unresponsive to major histocompatibility complex (MHC)–mismatched stimulators and suppress allogeneic responses by T cells in vitro. In addition, SHIP–/– CD4+CD25– T cells mediate reduced lethal GVHD on adoptive transfer to MHC-mismatched hosts. Furthermore, hosts with induced SHIP deficiency exhibit delayed rejection of MHC-mismatched cardiac grafts. Thus, SHIP is required for robust graft-versus-host and host-versus-graft responses by CD4+ T cell and limits their immunoregulatory capacity. These findings further define the immunosuppressive mechanisms that result from SHIP deficiency and provide additional justification for targeting SHIP in clinical transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Peng, P. Ye, D. J. Rawlings, H. D. Ochs, and C. H. Miao Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A mice after factor VIII plasmid-mediated gene therapy Blood, November 12, 2009; 114(20): 4373 - 4382. [Abstract] [Full Text] [PDF] S. Nagaraj, M. Collazo, C. A. Corzo, J.-I. Youn, M. Ortiz, D. Quiceno, and D. I. Gabrilovich Regulatory Myeloid Suppressor Cells in Health and Disease Cancer Res., October 1, 2009; 69(19): 7503 - 7506. [Full Text] [PDF] N. R. Locke, S. J. Patterson, M. J. Hamilton, L. M. Sly, G. Krystal, and M. K. Levings SHIP Regulates the Reciprocal Development of T Regulatory and Th17 Cells J. Immunol., July 15, 2009; 183(2): 975 - 983. [Abstract] [Full Text] [PDF]

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