期刊
NATURE IMMUNOLOGY
卷 18, 期 11, 页码 1218-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3847
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资金
- Intramural Research Program of the US National Institutes of Health
- National Cancer Institute
- Center for Cancer Research
- US National Institutes of Health [R01AI097244-01A1]
T cell antigen receptor (TCR) signaling in the thymus initiates positive selection, but the CD8(+)-lineage fate is thought to be induced by cytokines after TCR signaling has ceased, although this remains controversial and unproven. We have identified four cytokines (IL-6, IFN-gamma, TSLP and TGF-beta) that did not signal via the common gamma-chain (gamma(c)) receptor but that, like IL-7 and IL-15, induced expression of the lineage-specifying transcription factor Runx3d and signaled the generation of CD8(+) T cells. Elimination of in vivo signaling by all six of these 'lineage-specifying cytokines' during positive selection eliminated Runx3d expression and completely abolished the generation of CD8(+) single-positive thymocytes. Thus, this study proves that signaling during positive selection by lineage-specifying cytokines is responsible for all CD8(+)-lineage-fate 'decisions' in the thymus.
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