Reprogrammed Foxp3+ Regulatory T Cells Provide Essential Help to Support Cross-presentation and CD8+ T Cell Priming in Naive Mice

Madhav D. Sharma, De Yan Hou, Babak Baban, Pandelakis A. Koni, Yukai He, Phillip R. Chandler, Bruce R. Blazar, Andrew L. Mellor, David H. Munn

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Foxp3+ regulatory T (Treg) cells can undergo reprogramming into a phenotype expressing proinflammatory cytokines. However, the biologic significance of this conversion remains unclear. We show that large numbers of Treg cells undergo rapid reprogramming into activated T helper cells after vaccination with antigen plus Toll-like receptor 9 (TLR-9) ligand. Helper activity from converted Treg cells proved essential during initial priming of CD8+ T cells to a new cross-presented antigen. Help from Treg cells was dependent on CD40L, and (unlike help from conventional non-Treg CD4+ cells) did not require preactivation or prior exposure to antigen. In hosts with established tumors, Treg cell reprogramming was suppressed by tumor-induced indoleamine 2,3-dioxygenase (IDO) and vaccination failed because of lack of help. Treg cell reprogramming, vaccine efficacy, and antitumor CD8+ T cell responses were restored by pharmacologic inhibition of IDO. Reprogrammed Treg cells can thus participate as previously unrecognized drivers of certain early CD8+ T cell responses.

Original languageEnglish (US)
Pages (from-to)942-954
Number of pages13
JournalImmunity
Volume33
Issue number6
DOIs
StatePublished - Dec 14 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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