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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3285-3292. Prepublished online as a Blood First Edition Paper on June 23, 2005; DOI 10.1182/blood-2005-01-0410. This Article Full Text Full Text (PDF) Erratum (v107,p38) All Versions of this Article: 2005-01-0410v1 2005-01-0410v2 106/9/3285    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 Hubbard, V. M. Articles by van den Brink, M. R. M. Search for Related Content PubMed PubMed Citation Articles by Hubbard, V. M. Articles by van den Brink, M. R. M. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation Vanessa M. Hubbard, Jeffrey M. Eng, Teresa Ramirez-Montagut, Kartono H. Tjoe, Stephanie J. Muriglan, Adam A. Kochman, Theis H. Terwey, Lucy M. Willis, Rafaella Schiro, Glen Heller, George F. Murphy, Chen Liu, Onder Alpdogan, and Marcel R. M. van den Brink From the Department of Medicine and Immunology, Department of Pediatrics, and Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Pathology, Brigham and Women's Hospital, Boston, MA; and Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville. Inducible costimulator (ICOS) is expressed on activated and memory T cells and is involved in the regulation of cytokine production. We studied the role of ICOS on alloreactive T cells in graft versus host disease (GVHD) and determined that ICOS expression was up-regulated on alloreactive T cells in recipients of an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with GVHD. We compared ICOS-/- T cells with wild-type (WT) T cells in 2 GVHD models. In both models, recipients of ICOS-/- T cells demonstrated significantly less GVHD morbidity and mortality, which was associated with less intestinal and hepatic GVHD but increased cutaneous GVHD. In addition, recipients of ICOS-/- donor T cells displayed a slight decrease in graft versus leukemia (GVL) activity. Further analysis of alloreactive ICOS-/- T cells showed no defect in activation, proliferation, cytotoxicity, and target organ infiltration. Recipients of ICOS-/- T cells had decreased serum levels of interferon- (IFN-), while interleukin-4 (IL-4) and IL-10 levels were increased, suggesting that alloreactive ICOS-/- T cells are skewed toward T helper-2 (Th2) differentiation. These data suggest a novel role for ICOS in the regulation of Th1/Th2 development of activated T cells. In conclusion, alloreactive ICOS-/- donor T cells induce less GVHD due to a Th2 immune deviation while GVL activity is slightly diminished. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Socie and B. R. Blazar Acute graft-versus-host disease: from the bench to the bedside Blood, November 12, 2009; 114(20): 4327 - 4336. [Abstract] [Full Text] [PDF] M. Rotondi, L. Chiovato, S. Romagnani, M. Serio, and P. Romagnani Role of Chemokines in Endocrine Autoimmune Diseases Endocr. Rev., August 1, 2007; 28(5): 492 - 520. [Abstract] [Full Text] [PDF] Y. Nukada, N. Okamoto, S. Konakahara, K. Tezuka, K. Ohashi, K. Mizuno, and T. Tsuji AILIM/ICOS-mediated elongation of activated T cells is regulated by both the PI3-kinase/Akt and Rho family cascade Int. Immunol., December 1, 2006; 18(12): 1815 - 1824. [Abstract] [Full Text] [PDF] E. H. Wilson, C. Zaph, M. Mohrs, A. Welcher, J. Siu, D. Artis, and C. A. Hunter B7RP-1-ICOS Interactions Are Required for Optimal Infection-Induced Expansion of CD4+ Th1 and Th2 Responses J. Immunol., August 15, 2006; 177(4): 2365 - 2372. [Abstract] [Full Text] [PDF] X.-Z. Yu, Y. Liang, R. I. Nurieva, F. Guo, C. Anasetti, and C. Dong Opposing Effects of ICOS on Graft-versus-Host Disease Mediated by CD4 and CD8 T Cells. J. Immunol., June 15, 2006; 176(12): 7394 - 7401. [Abstract] [Full Text] [PDF]

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