Requirements for Selection of Conventional and Innate T Lymphocyte Lineages

SummaryMice deficient in the Tec kinase Itk develop a large population of CD8+ T cells with properties, including expression of memory markers, rapid production of cytokines, and dependence on Interleukin-15, resembling NKT and other innate T cell lineages. Like NKT cells, these CD8+ T cells can be selected on hematopoietic cells. We demonstrate that these CD8+ T cell phenotypes resulted from selection on hematopoietic cells—forcing selection on the thymic stroma reduced the number and innate phenotypes of mature Itk-deficient CD8+ T cells. We further show that, similar to NKT cells, selection of innate-type CD8+ T cells in Itk−/− mice required the adaptor SAP. Acquisition of their innate characteristics, however, required CD28. Our results suggest that SAP and Itk reciprocally regulate selection of innate and conventional CD8+ T cells on hematopoietic cells and thymic epithelium, respectively, whereas CD28 regulates development of innate phenotypes resulting from selection on hematopoietic cells.