Identification of lineage-specifying cytokines that signal all CD8 + -cytotoxic-lineage-fate 'decisions' in the thymus

Ruth Etzensperger, Tejas Kadakia, Xuguang Tai, Amala Alag, Terry I. Guinter, Takeshi Egawa, Batu Erman, Alfred Singer

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 languageEnglish
Pages (from-to)1218-1227
Number of pages10
JournalNature immunology
Issue number11
StatePublished - Oct 18 2017


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