Abstract
CD4 T helper lineage-commitment is initially determined during thymic selection and is driven by the key transcription factor ThPOK. Continuous expression of ThPOK is required to maintain mature MHC class II restricted CD4 T lymphocytes as T helper cells. Here we identify an activation induced differentiation process in vivo that is characterized by the silencing of Thpok and the generation of a new type of antigen-experienced CD4 T cells. This alternative differentiation also prevents activated CD4 T cells from becoming pro-inflammatory effector cells that could damage tissues. Therefore, the data show an unexpected plasticity in mature CD4 T lymphocytes, and define a new subtype of activated CD4 T cells characterized by the loss of the ThPOK-controlled T helper phenotype and the gain of cytotoxic and regulatory competence.
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