Immunity
Volume 37, Issue 4, 19 October 2012, Pages 622-633
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Article
The Transcription Factors Thpok and LRF Are Necessary and Partly Redundant for T Helper Cell Differentiation

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Summary

T helper (Th) cells are critical for defenses against infection and recognize peptides bound to class II major histocompatibility complex (MHC II) molecules. Although transcription factors have been identified that direct Th cells into specific effector fates, whether a “master” regulator controls the developmental program common to all Th cells remains unclear. Here, we showed that the two transcription factors Thpok and LRF share this function. Although disruption of both factors did not prevent the generation of MHC II-specific T cells, these cells failed to express Th cell genes or undergo Th cell differentiation in vivo. In contrast, T cells lacking Thpok, which only displayed LRF-dependent functions, contributed to multiple effector responses, both in vitro and in vivo, with the notable exception of Th2 cell responses that control extracellular parasites. These findings identify the Thpok-LRF pair as a core node of Th cell differentiation and function.

Highlights

► Thpok-deficient MHC II-restricted T cells have Th cell functions ► The transcription factor LRF promotes helper functions of Thpok-deficient cells ► Unlike Thpok, LRF does not support Th2 cell differentiation

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These authors contributed equally to this work