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Blood, 22 January 2009, Vol. 113, No. 4, pp. 945-952.
Prepublished online as a Blood First Edition Paper on October 17, 2008; DOI 10.1182/blood-2008-08-172155.
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Submitted August 5, 2008
Accepted September 25, 2008
IL-17 contributes to CD4-mediated graft-versus-host disease
Lucy W Kappel, Gabrielle L Goldberg, Christopher G King, David Y Suh, Odette M Smith, Cassandra Ligh, Amanda M. Holland, Jeremy Grubin, Nicholas M Mark, Chen Liu, Yoichiro Iwakura, Glen Heller, and Marcel RM van den Brink*
Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States
Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, United States
Department of Pathology, University of Florida College of Medicine, Gainesville, FL, United States
Center for Experimental Medicine, Institute of Medical Sciences, University of Tokyo, Tokyo, Japan
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, United States
* Corresponding author; email: vandenbm{at}mskcc.org.
CD4+IL-17+ T cells (Th17 cells) have been implicated in allograft rejection of solid organs and several autoimmune diseases. However, no studies have addressed the functional role of Th17 cells in the development of acute graft-versus-host disease (GVHD). We detected significant numbers of alloreactive CD4+ donor T cells expressing IL-17, IL-17F or IL-22 in the lymphoid organs of recipients of an allogeneic bone marrow transplant (BMT). We found no differences in GVHD mortality or graft-versus-tumor (GVT) activity between wild type (WT) and IL-17-/- T cell recipients. However, upon transfer of murine IL-17-/- CD4+ T cells in an allogeneic BMT model, GVHD development was significantly delayed compared to recipients of WT CD4+ T cells, yet overall GVHD mortality was unaffected. Moreover, recipients of IL-17-/- CD4+ T cells had significantly fewer Th1 cells during the early stages of GVHD. Furthermore, we observed a decrease in the number of IFN- -secreting macrophages and granulocytes and decreased production of proinflammatory cytokines (IFN-, IL-4 and IL-6) in recipients of IL-17-/- CD4+ T cells. We conclude that IL-17 is dispensable for GVHD and GVT activity by whole T cells, but contributes to the early development of CD4-mediated GVHD by promoting production of proinflammatory cytokines.
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