L-selectin is dispensable for T regulatory cell function postallogeneic bone marrow transplantation

Am J Transplant. 2010 Dec;10(12):2596-603. doi: 10.1111/j.1600-6143.2010.03319.x. Epub 2010 Nov 10.

Abstract

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation / immunology*
  • Cell Migration Assays
  • Graft vs Host Disease / prevention & control*
  • L-Selectin / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Chemokine / biosynthesis
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Receptors, Chemokine
  • L-Selectin