Thymus-derived innate CD8+CD44hi T cells display features of antigen-experienced T cells with bystander helper properties (153.43)

Abstract

Abstract Innate CD8 T cells are abundant in several transcription factors (TFs)-deficient mouse models, but little is known about their development in wild-type animals. We used the RAG2-GFP mouse model to discriminate between memory, naïve classic and innate TCRαβ CD8 cells in the thymus. Relative to classic T cells, innate thymocytes display increased levels of numerous cell surface molecules (TCR, CD2, CD3, CD5, CD38, CD62L, B7H1) and enhanced expression of the TFs T-bet, EOMES, Id3 and KFL2. Hematopoietic chimera studies revealed that non-hematopoietic MHCI+ cells are required for innate CD8 T cell selection in the thymus. Mice expressing the transgenic OTI TCR generate both classic and innate CD8 thymocytes suggesting that both subsets have overlapping TCR repertoires. Innate CD8 T cells were also found to rapidly produce high levels of IFNγ upon stimulation and to readily proliferate in response to IL2 and IL4. Under lymphopenic conditions, classic CD8 T cell expansion was 2-3 fold greater than that of innate T cells, which constitutively express B7H1 making them unduly susceptible to apoptosis. To test their bystander properties, we added classic or innate T cells as third-party cells to an in vitro antigen presentation assay. Innate T cells were capable of promoting the proliferation and activation of responding T cells in a CD44-dependent manner. These observations show that innate CD8 T cells represent a subset of thymocytes that differ in many ways from classic CD8 T cells.