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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3372-3380. Prepublished online as a Blood First Edition Paper on December 23, 2004; DOI 10.1182/blood-2004-10-3869. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-3869v1 105/8/3372    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 Taylor, P. A. Articles by Blazar, B. R. Search for Related Content PubMed PubMed Citation Articles by Taylor, P. A. Articles by Blazar, B. R. Related Collections Immunobiology Transplantation Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM) Patricia A. Taylor, Angela Panoskaltsis-Mortari, Gordon J. Freeman, Arlene H. Sharpe, Randolph J. Noelle, Alexander Y. Rudensky, Tak W. Mak, Jonathan S. Serody, and Bruce R. Blazar From the University of Minnesota Cancer Center and Department of Pediatrics, Division of BMT, Minneapolis, MN; the USA Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; the Department of Pathology, Brigham and Women's Hospital, Boston, MA; the Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH; the Department of Immunology, University of Washington School of Medicine, Seattle, WA; the Department of Medical Biophysics and Immunology, Advanced Medical Discovery Institute, Toronto, ON; and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC. Inducible costimulator (ICOS), a CD28/cytotoxic T lymphocyte antigen 4 (CTLA-4) family member, is expressed on activated T cells. ICOS ligand, a B7 family member, is constitutively expressed on B cells, macrophages, and dendritic cells and is up-regulated on antigen-presenting cells (APCs) and some nonlymphoid tissues by tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Thus, ICOS: ICOS ligand (ICOSL) blockade could reduce alloreactive T cell-APC interactions responsible for graft-versus-host disease (GVHD) and bone marrow (BM) graft rejection. ICOS blockade, achieved with ICOS-/- mice or anti-ICOS monoclonal antibody (mAb) administration, resulted in significant inhibition of GVHD in multiple strain combinations whether mediated by CD4+ and/or CD8+ T cells, alloantigen-specific T-cell receptor (TCR) transgenic (Tg) T cells, or CD28-, T helper 1 (Th1)-, or Th2-deficient T cells. Anti-ICOS significantly delayed GVHD mortality even when mAb infusions were delayed until day 5 after transplantation. ICOS blockade reduced the number of alloantigen-specific effector cells but did not prevent their activation. Imaging of green fluorescent protein-positive (GFP+) effectors indicated that ICOS blockade inhibited expansion of GVHD-causing effector T cells in secondary lymphoid and GVHD target organs. Engraftment rates were significantly higher in ICOS-/- versus wild-type (WT) mice receiving allogeneic BM, and ICOS blockade significantly inhibited expansion of host antidonor alloantigen-specific BM graft-rejecting T cells. These data suggest that the ICOS pathway may be a beneficial therapeutic target for GVHD inhibition, GVHD therapy, and BM graft promotion. (Blood. 2005; 105:3372-3380) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: ICOS: a new important player in BMT Yair Reisner Blood 2005 105: 3006-3007. [Full Text] [PDF] This article has been cited by other articles: T. Yamashita, H. Tamura, C. Satoh, E. Shinya, H. Takahashi, L. Chen, A. Kondo, T. Tsuji, K. Dan, and K. Ogata Functional B7.2 and B7-H2 Molecules on Myeloma Cells Are Associated with a Growth Advantage Clin. Cancer Res., February 1, 2009; 15(3): 770 - 777. [Abstract] [Full Text] [PDF] B. Peng, P. Ye, B. R. Blazar, G. J. Freeman, D. J. Rawlings, H. D. Ochs, and C. H. Miao Transient blockade of the inducible costimulator pathway generates long-term tolerance to factor VIII after nonviral gene transfer into hemophilia A mice Blood, September 1, 2008; 112(5): 1662 - 1672. [Abstract] [Full Text] [PDF] A. H.-M. Tan, S. Y.-P. Goh, S.-C. Wong, and K.-P. Lam T Helper Cell-specific Regulation of Inducible Costimulator Expression via Distinct Mechanisms Mediated by T-bet and GATA-3 J. Biol. Chem., January 4, 2008; 283(1): 128 - 136. [Abstract] [Full Text] [PDF] M. P. Watson, A. J. T. George, and D. F. P. Larkin Differential effects of costimulatory pathway modulation on corneal allograft survival. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3417 - 3422. [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] V. M. Hubbard, J. M. Eng, T. Ramirez-Montagut, K. H. Tjoe, S. J. Muriglan, A. A. Kochman, T. H. Terwey, L. M. Willis, R. Schiro, G. Heller, et al. Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation Blood, November 1, 2005; 106(9): 3285 - 3292. [Abstract] [Full Text] [PDF]

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