Runx3 Regulates Integrin E/CD103 and CD4 Expression during Development of CD4/CD8 T Cells1

During thymic T cell development, immature CD4CD8 double-positive (DP) thymocytes develop either into CD4CD8 Th cells or CD4CD8 CTLs. Differentially expressed primary factors inducing the fate of these cell types are still poorly described. The tran-scription factor Runx3/AML-2 Runx, rust dominant factor; AML, acute myeloid leukemia is expressed specifically during the devel-opment of CD8 single-positive (SP) thymocytes, where it silences CD4 expression. Deletion of murine Runx3 results in a reduction of CD8 SP T cells and concomitant accumulation of CD4CD8 T cells, which cannot down-regulate CD4 expression in the thymus and periphery. In this study we have investigated the role of Runx3 during thymocyte development and CD4 silencing and have identified integrin E/CD103 on CD8 SP T cells as a new potential target gene of Runx3. We demonstrate that Runx3 is necessary not only to repress CD4, but also to induce CD103 expression during development of CD8 SP T cells. In addition, transgenic overexpression of Runx3 reduced CD4 expression during development of DP thymocytes, leading to a reduced number of CD4 SP thymocytes and an increased number of CD8 SP thymocytes. This reversal is not caused by redirection of specific MHC class II-restricted cells to the CD8 lineage. Overexpression of Runx3 also up-regulated CD103 expression on a subpopulation of CD4 SP T cells with characteristics of regulatory T cells. Thus, Runx3 is a main regulator of CD4 silencing and CD103 induction and thus contributes to the phenotype of CD8 SP T cells during thymocyte development. The Journal of Immunology, 2005, 175: 1694–1705. D uring T cell development in the thymus CD4CD8double-positive (DP)9 thymocytes undergo positive andnegative selection depending on the ability of their TCR to interact with thymic stromal cells presenting self-peptide