Innate-like CD8+ T cells with a memory surface marker phenotype that can be rapidly activated without previous antigen exposure have been described in mice that lack the Tec family kinases interleukin-2-inducible T cell kinase (ITK) and resting lymphocyte kinase (RLK). Decreased T cell receptor (TCR) signal strength in the absence of ITK and/or RLK is proposed to allow escape of these cells from negative selection in the thymus. Positive selection is thought to occur on haematopoietic cells that induce the innate-like phenotype of CD8+ T cells through homotypic signalling lymphocytic activation molecule (SLAM) receptor interactions with thymocytes and signalling through SLAM-associated adaptor protein (SAP). However, this new study shows that innate-like CD8+ T cells can undergo positive selection on non-haematopoietic cells in the thymus, in a similar manner to conventional T cells, and that the dependence on SLAM–SAP signalling is not intrinsic to CD8+ T cells.
Inhibitor of DNA binding protein 3 (ID3), an antagonist of E protein transcription factors, is induced downstream of signalling by Tec family kinases, and Id3−/− CD8+ thymocytes were shown to have an innate-like phenotype similar to that of Itk−/− or Rlk−/− CD8+ thymocytes. However, unlike Itk−/− or Rlk−/− CD8+ thymocytes, which were reported to be selected by haematopoietic cells expressing MHC class I molecules, the authors showed using bone-marrow chimeric mice that MHC class I expression by non-haematopoietic thymic epithelial cells (TECs), but not haematopoietic cells, was required for Id3−/− CD8+ thymocytes to develop the innate-like phenotype.
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