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Immunity. 2010 Dec 14;33(6):942-54. doi: 10.1016/j.immuni.2010.11.022. Epub 2010 Dec 9.

Reprogrammed foxp3(+) regulatory T cells provide essential help to support cross-presentation and CD8(+) T cell priming in naive mice.

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Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA; Immunotherapy Center, Medical College of Georgia, Augusta, GA 30912, USA.


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.

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