The cKrox transgene affects the development and function of multiple T cell types. (64.10)

Abstract

The zinc finger transcription factor cKrox is crucial for CD4 T cell development. Mice lacking a functional cKrox gene lack CD4 T cells. Furthermore, in cKrox-deficient mice, developing T cells expressing a MHC class II-restricted TCR are redirected into the CD8 T cell lineage. We investigated the effect of the cKrox transgene on the development and function of two other types of T cells, namely self-specific CD8 T cells and CD4 T regulatory cells. In TCR transgenic mice that express a male-specific TCR (H-Y TCR), the only CD8 T cells that developed in male TCR transgenic mice are self-specific CD8 T cells. These H-Y TCR+ self-specific CD8 T cells are characterized by high expression of CD44, CD122, Ly6C, 1B11, NK cell markers and proliferative response in response to IL-2 or IL-15. We found that the cKrox transgene converted these self-specific CD8 T cells into CD4 T cells. Furthermore, the converted CD4 T cells lost the characteristics of these self-specific CD8 T cells described above. Notably, the converted self-specific CD8 T cells express genes that are characteristic of CD4 T cells (GATA-3 and IL-2). The numbers of CD4 T regulatory cells were significantly higher in cKrox transgenic mice and these cells expressed higher suppressor activity compared to CD4 T regulatory cells from control mice. These studies indicate that the cKrox transgene affects the development and function of multiple T cell types. This work is supported by the Canadian Cancer Society.