Attenuation of Acute Graft-versus-Host Disease in the Absence of the Transcription Factor ROR gamma t

作者：Fulton LeShara M; Carlson Michael J; Coghill James M; Ott Laura E; West Michelle L; Panoskaltsis Mortari Angela; Littman Dan R; Blazar Bruce R; Serody Jonathan S^*

来源：The Journal of Immunology, 2012, 189(4): 1765-1772.

DOI：10.4049/jimmunol.1200858

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.

• 出版日期2012-8-15