SAP Protein-Dependent Natural Killer T-like Cells Regulate the Development of CD8+ T Cells with Innate Lymphocyte Characteristics

Summary: 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. [ABSTRACT FROM AUTHOR]