T cell differentiation in the thymus is dependent on signaling by both T cell antigen receptors and by cytokine receptors. Our current understanding of how lineage choice is determined in the thymus is built around the concept that signaling by the T cell antigen receptor prevents signaling by cytokine receptors, and that cytokine signaling only occurs after signaling by the T cell antigen receptor has ceased. Despite its central role in T cell development, it is not known how T cell antigen receptor signaling 'desensitizes'the cytokine receptor so that it is no longer able to transmit signals into the cell. Consequently, we have undertaken a systematic examination of the molecular basis by which cytokine receptor signaling is impaired by TCR signals in developing T cells in the thymus and in mature T cells in the periphery.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011117-06
Application #
8763355
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$244,735
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Kimura, Motoko Y; Pobezinsky, Leonid A; Guinter, Terry I et al. (2013) IL-7 signaling must be intermittent, not continuous, during CD8? T cell homeostasis to promote cell survival instead of cell death. Nat Immunol 14:143-51