TGFβ1 deficiency does not affect the generation and maintenance of CD4+CD25+FOXP3+ putative Treg cells, but causes their numerical inadequacy and loss of regulatory function

Ramireddy Bommireddy, George F. Babcock, Ram R. Singh, Thomas C Doetschman

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

TGFβ1 is considered to be required for peripheral maintenance of CD4+CD25+FOXP3+ Treg cells. However, we demonstrate no reduction in the percentage of such T cells in the spleens and thymi of Tgfb1-/- mice. Although putative Treg cells, characterized as CD4+CD25+FOXP3+CD62L+ T cells, are increased in Tgfb1-/- mice, they may be inadequate to control activated T cells since the ratio of activated T cells:putative Treg cells is several-fold higher in Tgfb1-/- mice than in control mice. We further show that whereas Tgfb1-/- mice that express a chicken OVA-specific TCR transgene (DO11.10) have an increase in putative Treg cells, there are no detectable CD4+CD25+ T cells in the spleens of DO11.10 Rag1-/- mice suggesting that Treg-cell generation is self-antigen dependent regardless of whether they express Tgfb1. Finally, we demonstrate that Tgfb1-/- T cells remain responsive to the suppressive effect of TGFβ1 in vitro. These data suggest that TGFβ1 is required for the regulatory function of Treg cells to prevent activation of T cells and autoimmunity.

Original languageEnglish (US)
Pages (from-to)206-213
Number of pages8
JournalClinical Immunology
Volume127
Issue number2
DOIs
Publication statusPublished - May 2008

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Keywords

  • Autoimmunity
  • DO11.10
  • FOXP3
  • Inflammation
  • Knockout mice
  • T cells
  • TGFβ1
  • Tolerance

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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