期刊
JOURNAL OF IMMUNOLOGY
卷 189, 期 4, 页码 1765-1772出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1200858
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资金
- National Institutes of Health [R01 AI064363, R56 AI082219, R01 HL56067, R01 AI34495, R01 CA72669, T32HL007149, K12CA120780, T32CA009156, F31AI096900]
- Mary Elizabeth Thomas Endowment Fund
Graft-versus-host disease (GVHD) remains the most significant complication after allogeneic stem cell transplantation. Previously, acute GVHD had been considered to be mediated predominantly by Th1-polarized T cells. Recently, investigators have identified a second proinflammatory lineage of T cells termed Th17 that is critically dependent on the transcription factor retinoic acid-related orphan receptor (ROR)gamma t. In this study, we have evaluated the role of Th17 cells in murine acute GVHD by infusing donor T cells lacking RORC and as a consequence the isoform ROR gamma t. Recipients given donor CD4(+) and CD8(+) T cells lacking RORC had significantly attenuated acute GVHD and markedly decreased tissue pathology in the colon, liver, and lung. Using a clinically relevant haploidentical murine transplantation model, we showed that RORC-/- CD4(+) T cells alone diminished the severity and lethality of acute GVHD. This was not found when CD4(+) T cells from RORC-/- mice were given to completely mismatched BALB/c mice, and it was correlated with absolute differences in the generation of TNF in the colon after transplant. Thus, CD4(+) T cell expression of RORC is important in the pathogenesis of acute GVHD. The Journal of Immunology, 2012, 189: 1765-1772.
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