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Runx3 regulates integrin alpha E/CD103 and CD4 expression during development of CD4-/CD8+ T cells

Authors: 
Grueter B, Petter M, Egawa T, Laule-Kilian K, Aldrian CJ, Wuerch A, Ludwig Y, Fukuyama H, Wardemann H, Waldschuetz R, Moroy T, Taniuchi I, Steimle V, Littman DR, Ehlers M
Citation: 
J Immunol. 2005 Aug 1;175(3):1694-705. Erratum in: J Immunol. 2005 Nov 1;175(9):6238
Abstract: 
During thymic T cell development, immature CD4+CD8+ double-positive (DP) thymocytes develop either into CD4+CD8- Th cells or CD4-CD8+ CTLs. Differentially expressed primary factors inducing the fate of these cell types are still poorly described. The transcription factor Runx3/AML-2 Runx, runt [corrected] dominant factor; AML, acute myeloid leukemia is expressed specifically during the development 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 CD4+CD8+ 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 alpha(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.
Organism or Cell Type: 
cell culture: immature thymocytes, CD4- CD8+ cells
Delivery Method: 
Electroporation