Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells

Nat Med. 2013 Jun;19(6):739-46. doi: 10.1038/nm.3179. Epub 2013 Apr 28.

Abstract

CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / analysis*
  • Antigens, CD / genetics
  • Cell Separation
  • Humans
  • Integrin alpha2 / analysis*
  • Mice
  • Mice, Inbred C57BL
  • Nippostrongylus
  • Strongylida Infections / immunology
  • T-Lymphocytes, Regulatory / chemistry
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology
  • Transcriptome

Substances

  • Antigens, CD
  • CD223 antigen
  • Integrin alpha2

Associated data

  • GEO/GSE53514