CD8+ T cells are selected via low-affinity interaction with MHC class I molecules on thymic epithelial cells (TECs). However, compromised T cell receptor signaling was proposed to force CD8+ T cell selection on hematopoietic cells through a SLAM-associated protein (SAP)-dependent mechanism similar to NKT cells. The outcome is an unconventional CD8+ T cell with phenotypic and functional characteristics of innate lymphocytes. Here we showed that Id3−/− CD8+ T cells had an innate-like phenotype and required SAP for their development. However, like conventional CD8+ T cells, Id3−/− CD8+ thymocytes were selected on TECs. The requirement for SAP and the innate-like phenotype was not intrinsic to Id3−/− CD8+ thymocytes. Rather, an expanded population of NKT-like cells induced the innate phenotype on CD8+ T cells through production of interleukin-4. Our findings reveal that accumulation of NKT-like cells promotes conventional CD8+ thymocytes to acquire innate lymphocyte characteristics.
Highlights
► CD8 T cells in Id3−/− mice have an innate-like phenotype ► The innate-like CD8 phenotype is not CD8 cell intrinsic ► NKT-like cells induce the innate-like phenotype on CD8 T cells in Id3−/− mice ► NKT-like cell-produced IL-4 is the mediator of the innate-like CD8 T cell phenotype
