In murine models, the adoptive transfer of CD4+/CD25+ regulatory T cells (Tregs) inhibited graft-versus-host disease (GvHD). Previous work has indicated a critical role for the adhesion molecule L-selectin (CD62L) in the function of Tregs in preventing GvHD. Here we examined the capacity of naive wild-type (WT), CD62L-/- and ex vivo expanded CD62LLo Tregs to inhibit acute GvHD. Surprisingly, we found that CD62L-/- Tregs were potent suppressors of GvHD, whereas CD62LLo Tregs were unable to inhibit disease despite being functionally competent to suppress allo T cell responses in vitro. Concomitant with improved outcomes, WT and CD62L -/- Tregs significantly reduced liver pathology and systemic pro-inflammatory cytokine production, although CD62L-/- Tregs were less effective in reducing lung pathology. While accumulation of CD62L-/- Tregs in GvHD target organs was equivalent to WT Tregs, CD62L-/- Tregs did not migrate as well as WT Tregs to peripheral lymph nodes (PLNs) over the first 2 weeks posttransplantation. This work demonstrated that CD62L was dispensable for Treg-mediated protection from GvHD.
Copyright 2011 Elsevier B.V., All rights reserved.
- Allogeneic stem cell transplantation
- regulatory T cells