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

M. J. Carlson, L. M. Fulton, J. M. Coghill, M. L. West, J. E. Burgents, Y. Wan, A. Panoskaltsis-Mortari, T. F. Tedder, B. R. Blazar, J. S. Serody

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2596-2603
Number of pages8
JournalAmerican Journal of Transplantation
Volume10
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • Allogeneic stem cell transplantation
  • CD62L
  • GvHD
  • regulatory T cells

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