Role of T cell subsets in promoting intestinal GVHD. (145.4)

Abstract

Abstract The relative contributions of CD4 vs. CD8 T cell subsets in graft-versus-host disease (GVHD) remains poorly defined. Previous studies in this lab have shown that the integrin CD103 is required for accumulation of CD8 T cells in epithelial compartments and concomitant epithelial injury during GVHD in MHC-mismatched transplant models. The goal of the present study was to define the role of the CD103 pathway in promoting GVHD following MHC-matched BMT, the most common clinical scenario. Our data showed no difference in the ability of WT or CD103-/- splenocytes to cause acute GVHD mortality in this transplant scenario. However, depletion of CD4 T cells on day 6 post transplant completely prevented acute GVHD mortality, despite a robust CD8 T cell response. These data suggested that acute gut injury and mortality elicited following BMT are mediated by CD4 T cells rather than CD8 T cells as is commonly assumed. Consistent with this hypothesis, CD4 depletion also prevented acute mortality following MHC-mismatched transplant. FACS analyses of long-surviving hosts in this model revealed that T cells infiltrating the host gut epithelium were initially CD103- but progressively acquired CD103 expression concomitant with progressive epithelial injury. These data indicate that CD103 is preferentially expressed by CD8 T cells at late post-transplant intervals, and that effective blockade of GVHD pathology will likely require combined blockade of the CD4 and CD103 pathways.