Human CD25+CD4+ T suppressor cell clones produce transforming growth factor β, but not interleukin 10, and are distinct from type 1 T regulatory cells

Megan K. Levings, Romina Sangregorio, Claudia Sartirana, Anna Lisa Moschin, Manuela Battaglia, Paul C. Orban, Maria Grazia Roncarolo

Research output: Contribution to journalArticlepeer-review

Abstract

T regulatory (Tr) cells are essential for the induction of peripheral tolerance. Several types of Tr cells exist, including CD4+ T cells which express CD25 constitutively and suppress immune responses via direct cell-to-cell interactions, and type 1 T regulatory (Tr1) cells, which function via secretion of interleukin (IL)-10 and transforming growth factor (TGF)-β. The relationship between CD25+CD4+ T cells and Tr1 cells remains unclear. Here, we demonstrate at the clonal level that Tr1 and CD25+CD4+ T cells are two distinct subsets of regulatory cells with different cytokine production profiles. Furthermore, CD25+CD4+ T cells can be rendered anergic by IL-10 and differentiated into Tr1 cells in the absence of CD25+CD4+ T cells. Cloned human CD25+CD4+ T cell populations are heterogeneous and only a subset of clones continues to express high levels of CD25 and is suppressive. The intensity of CD25, cytotoxic T lymphocyte antigen (CTLA)-4, and glucocorticoid-induced tumor necrosis factor (TNF) receptor expression correlates with the suppressive capacity of the T cell clones. None of the CD25+CD4+ T cell clones with suppressive function produce IL-10, but all produce TGF-β. Suppression mediated by CD25+CD4+ T cell clones is partially dependent on TGF-β, but not on constitutive high expression of CD25. Together these data indicate that naturally occurring human CD25+CD4+ T cells are distinct from IL-10-producing Tr1 cells.

Original languageEnglish
Pages (from-to)1335-1346
Number of pages12
JournalJournal of Experimental Medicine
Volume196
Issue number10
DOIs
Publication statusPublished - Nov 18 2002

Keywords

  • IL-10
  • Interleukin 2 receptor α chain
  • Suppressor T lymphocytes
  • TGF-β
  • Tr1

ASJC Scopus subject areas

  • Immunology

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