CD4+ CD25+ CD62+ T-Regulatory Cell Subset Has Optimal Suppressive and Proliferative Potential

Shuang Fu, Adam C. Yopp, Xia Mao, Dongmei Chen, Nan Zhang, Dan Chen, Minwei Mao, Yaozhong Ding, Jonathan S. Bromberg

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

CD4+ CD25+ regulatory T cells (Treg) are potent suppressors, and play important roles in autoimmunity and transplantation. Recent reports suggest that CD4+ CD25+ Treg are not a homogeneous cell population, but the differences in phenotype, function, and mechanisms among different subsets are unknown. Here, we demonstrate CD4 + CD25+ Treg cells can be divided into subsets according to cell-surface expression of CD62L. While both subsets express foxp3 and are anergic, the CD62L+ population is more potent on a per cell basis, and proliferates and maintains suppressive function far better than the CD62L- population and unseparated CD4+ CD25+ Treg. The CD62L + population preferentially migrates to CCL19, MCP-1 and FTY720. Both CD62L+ and CD62L- subsets prevent the development of autoimmune gastritis and colitis induced by CD4+ CD25-CD45RBhigh cells in severe combined immunodeficiency (SCID) mice. Overall, these results suggest CD4+ CD25+ Treg are not a homogenous cell population, but can be divided into at least two subsets according to CD62L expression. The CD62L+ subset is a more potent suppressor than the CD62L- population or unfractionated CD4+ CD25+ Treg cells, can be expanded far more easily in culture, and is more responsive to chemokine-driven migration to secondary lymphoid organs. These properties may have significant implications for the clinical manipulation of the CD4 + CD25+ CD62L+ cells.

Original languageEnglish (US)
Pages (from-to)65-78
Number of pages14
JournalAmerican Journal of Transplantation
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 2004

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Keywords

  • CD4 CD25 Treg
  • L-selectin
  • Suppression

ASJC Scopus subject areas

  • Immunology

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