IL-17 contributes to CD4-mediated graft-versus-host disease Journal Article
| Authors: | Kappel, L. W.; Goldberg, G. L.; King, C. G.; Suh, D. Y.; Smith, O. M.; Ligh, C.; Holland, A. M.; Grubin, J.; Mark, N. M.; Liu, C.; Iwakura, Y.; Heller, G.; Den Brink, M. R. M. V. |
| Article Title: | IL-17 contributes to CD4-mediated graft-versus-host disease |
| Abstract: | CD4<sup>+</sup> interleukin-17 (IL-17)<sup>+</sup> T cells (Th17 cells) have been implicated in allograft rejection of solid organs and several auto- immune diseases. However, the func- tional role of Th 17 cells in the develop- ment of acute graft-versus-host disease (GVHD) has not been well-characterized. We detected significant numbers of allo- reactive CD4<sup>+</sup> donor T cells expressing IL-17, IL-17F, or IL-22 in the lymphoid organs of recipients of an allogeneic bone marrow transplant. We found no differ- ences in GVHD mortality or graft-versus- tumor (GVT) activity between wild type (WT) and IL-17 <sup>-/-</sup> T-cell recipients. How- ever, upon transfer of murine IL-17 <sup>-/-</sup>CD4<sup>+</sup> T cells in an allogeneic BMT model, GVHD development was significantly de- layed behind recipients of WT CD4<sup>+</sup> T cells, yet overall GVHD mortality was unaffected. Moreover, recipients of IL- 17<sup>-</sup>'<sup>-</sup> CD4<sup>+</sup> T cells had significantly fewer Th1 cells during the early stages of GVHD. Furthermore, we observed a decrease in the number of IFN-7-secreting macro- phages and granulocytes and decreased production of proinflammatory cytokines (interferon [IFN]-?, IL-4, and IL-6) in recipi- ents of IL-17<sup>-/-</sup> CD4<sup>+</sup> T cells. We con- clude 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 pro- duction of proinflammatory cytokines. © 2009 by The American Society of Hematology. |
| Keywords: | controlled study; protein expression; transplantation, homologous; genetics; disease course; mortality; nonhuman; cell proliferation; animal cell; mouse; animal; cytology; metabolism; mouse mutant; animals; mice; mice, knockout; animal tissue; spleen; interleukin 4; animal experiment; animal model; allogenic bone marrow transplantation; wild type; blood; immunology; donor; gamma interferon; cd4+ t lymphocyte; cd4-positive t-lymphocytes; graft versus host reaction; interleukin 6; cytokine production; cell count; interleukin 17; interferon-gamma; interleukin-17; cd4 antigen; th1 cell; macrophage; bone marrow transplantation; graft vs host disease; lymphocyte; lymphocytes; graft versus leukemia effect; graft recipient; interleukin 17f; interleukin 22; interleukin derivative; interleukin-22; cell transfer; granulocyte; lymphoid organ; allotransplantation; interleukins |
| Journal Title: | Blood |
| Volume: | 113 |
| Issue: | 4 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2009-01-22 |
| Start Page: | 945 |
| End Page: | 952 |
| Language: | English |
| DOI: | 10.1182/blood-2008-08-172155 |
| PUBMED: | 18931341 |
| PROVIDER: | scopus |
| PMCID: | PMC2630280 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 34" - "Export Date: 30 November 2010" - "CODEN: BLOOA" - "Source: Scopus" |
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