Agonist-driven development of CD4+CD25+Foxp3 + regulatory T cells requires a second signal mediated by Stat6

Vanesa Sanchez-Guajardo, Corinne Tanchot, John T. O'Malley, Mark H. Kaplan, Sylvie Garcia, Antonio A. Freitas

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The factors that induce Foxp3 expression and regulatory T (Treg) cell development remain unknown. In this study, we investigated the role of STAT4 and STAT6 in agonist-driven generation of Ag-specific Foxp3-expressing Treg cells. Our findings indicate that fully efficient induction of Foxp3 expression and development of Ag-specific Treg cells requires the synergistic action of two signals: a TCR-mediated signal and a second signal mediated by STAT6. Indeed, by comparing the development of wild-type and STAT4- and STAT6-deficient hemagglutinin-specific T cells in the presence of hemagglutinin Ag, we found that the absence of STAT6 impaired the generation of Ag-specific CD4 +CD25+Foxp3+ cells. Moreover, in transgenic mice expressing a constitutively active form of STAT6, we found that the fraction of CD4+Foxp3+ cells exceeds that of control wild-type littermates. Overall these findings support a role for the STAT6 pathway in Treg cell development and maintenance.

Original languageEnglish (US)
Pages (from-to)7550-7556
Number of pages7
JournalJournal of Immunology
Issue number12
StatePublished - Jun 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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