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ThPOK derepression is required for robust CD8 T cell responses to viral infection.


ABSTRACT: In the thymus, the transcription factor ThPOK is essential for the development of the CD4 helper T cell lineage, whereas active repression of ThPOK is critical for the development of the CD8 cytotoxic T cell lineage. ThPOK gene silencing is thought to be irreversible in peripheral CD8 T cells. We noticed that ThPOK repression is readily abrogated upon in vitro TCR stimulation of peripheral CD8 T cells. This observation prompted us to investigate a role for ThPOK in the CD8 T cell response to an acute viral infection. We observed that a functional deficiency of ThPOK does not affect CD8 T cell differentiation into effector T cells and the long-term persistence of Ag-specific memory T cells. However, in the absence of functional ThPOK, clonal expansion is significantly less in both primary and secondary CD8 T cell responses. Long-lived, Ag-specific CD8 T cells with a functional deficiency in ThPOK fail to produce high amounts of IL-2 and also fail to express high levels of granzyme B upon rechallenge. Our data reveal an unexpected role for ThPOK in CD8 T cells in promoting expansion and boosting the response to antigenic challenge.

SUBMITTER: Setoguchi R 

PROVIDER: S-EPMC2774709 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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ThPOK derepression is required for robust CD8 T cell responses to viral infection.

Setoguchi Ruka R   Taniuchi Ichiro I   Bevan Michael J MJ  

Journal of immunology (Baltimore, Md. : 1950) 20090904 7


In the thymus, the transcription factor ThPOK is essential for the development of the CD4 helper T cell lineage, whereas active repression of ThPOK is critical for the development of the CD8 cytotoxic T cell lineage. ThPOK gene silencing is thought to be irreversible in peripheral CD8 T cells. We noticed that ThPOK repression is readily abrogated upon in vitro TCR stimulation of peripheral CD8 T cells. This observation prompted us to investigate a role for ThPOK in the CD8 T cell response to an  ...[more]

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