Abstract
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-3, TSLP and TGF-β) that did not signal via the common 3-chain (3 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.
Original language | English |
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Pages (from-to) | 1218-1227 |
Number of pages | 10 |
Journal | Nature immunology |
Volume | 18 |
Issue number | 11 |
DOIs | |
State | Published - Oct 18 2017 |