ThPOK derepression is required for robust CD8 T cell responses to viral infection.
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.
Setoguchi
Ruka
R
Department of Immunology and the Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Taniuchi
Ichiro
I
Bevan
Michael J
MJ
D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D055879:Gene Knock-In Techniques; D007156:Immunologic Memory / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014157:Transcription Factors / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D014157:Transcription Factors; C497211:Zbtb7b protein, mouse