Encephalitogenic T cells that stably express both T-bet and RORγt consistently produce IFNγ but have a spectrum of IL-17 profiles

Th1/Thl7 cells, secreting both IFN gamma and IL-17, are often associated with inflammatory pathology. We cloned and studied the cytokine phenotypes of MBP-specific, TCR-identical encephalitogenic CD4+ cells in relationship to Th1- and Th17-associated transcription factors T-bet and ROR gamma t. IFN gamma-producing cells could be sub-divided into those that are T-bet(+)/ROR gamma t(-) and those that are T-bet(+)/ROR gamma t(+). The latter comprises a spectrum of phenotypes, as defined by IL-17 production, and can be induced to up-regulate IL-23R with IL-12 or IL-23. The former, bona fide Th1 cells, lack IL-23R expression under all conditions. In vivo, T-bet(+)/ROR gamma t(-) and T-bet(+)/ROR gamma t(+) clones induce EAE equally well. (C) 2009 Elsevier B.V. All rights reserved.