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Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-01-0192. This Article Full Text (PDF) All Versions of this Article: 2003-01-0192v1 103/2/717    most recent Alert me when this article is cited Alert me if a correction is posted 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 Jordan, W. J Articles by Ritter, M. A Search for Related Content PubMed PubMed Citation Articles by Jordan, W. J Articles by Ritter, M. A Social Bookmarking                   What's this? Submitted January 22, 2003 Accepted August 6, 2003 IL-13 production by donor T cells is prognostic of acute graft-versus-host disease following unrelated donor stem cell transplantation William J Jordan*, Paul A Brookes, Richard M Szydlo, John M Goldman, Robert I Lechler, and Mary A Ritter Department of Immunology, Imperial College London, London, United Kingdom Department of Haematology, Imperial College London, London, United Kingdom * Corresponding author; email: w.jordan1{at}ic.ac.uk. Despite the success of HLA-typing in allogeneic Stem Cell Transplantation (SCT) it is rare to find an unrelated donor that is perfectly matched, making identification of permissive mismatches of paramount importance. Here, we describe novel associations between production of cytokines by donor T cells and the subsequent development of acute Graft-versus-Host Disease (aGvHD). The data demonstrate a previously unreported link between Th2-type cytokines and aGvHD. An assay was established, based on cytokine production during the Mixed Lymphocyte Reaction that could detect both class-I class-II differences and was sensitive enough to discriminate between potential unrelated SCT donors identified through HLA-matching. This assay was then used to retrospectively examine associations between pre-SCT donor-anti-patient cytokine responses and aGvHD. Associations between IL-13 levels and aGvHD were by far the strongest predictor of aGvHD (p=0.0002). All patients suffering severe (grade III) aGvHD following SCT had donors that produced very high pre-transplant IL-13 responses, whilst those developing little or no aGvHD (grade 0-1) produced no IL-13 at all. IL-13 levels were independent of all other cytokines measured as well as CTLp frequencies. The cytokines IL-5, IFN- and TNF- also predicted development of aGvHD (p0.05 for all three), appearing to be co-produced in the assay and correlating with estimated CTLp frequencies. The data challenge the notion that aGvHD is purely a Th1-type cytokine driven response, highlighting a novel and highly significant link between the Th2-type cytokine IL-13 and aGvHD. Furthermore, this assay may represent a potentially useful tool for identification of permissible unrelated SCT donors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. D. L. Savage, T. de Boer, K. V. Walburg, S. A. Joosten, K. van Meijgaarden, A. Geluk, and T. H. M. Ottenhoff Human Anti-Inflammatory Macrophages Induce Foxp3+GITR+CD25+ Regulatory T Cells, Which Suppress via Membrane-Bound TGF{beta}-1 J. Immunol., August 1, 2008; 181(3): 2220 - 2226. [Abstract] [Full Text] [PDF] J. H. Gerrits, J. van de Wetering, S. Postma, J. J. M. Drabbels, L. M. B. Vaessen, J. N. M. IJzermans, J. Rischen, F. H. J. Claas, W. Weimar, and N. 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