Altered CD4/CD8 cell fate decision in the absence of MAZR due to redirected differentiation of MHC class I-restricted thymocytes (85.9)

Abstract

Abstract Cell fate specifications during thymocyte differentiation are linked with the tightly controlled expression of CD4 and CD8. We have previously identified that the transcriptional regulator MAZR is an important regulator of the activation of the Cd8ab gene complex during the DN to DP transition. To investigate the role of MAZR in more detail, MAZR-/- mice were generated. MAZR-/- mice were smaller in size and were born at reduced mendelian frequency. MAZR-/- DN thymocytes did not show premature expression of CD8, indicating that the deletion of MAZR is not sufficient to activate CD8 expression in DN cells. However, variegated CD8 expression in DP thymocytes of Cd8 enhancer E8I,E8II doubly deficient mice was dramatically reduced in the absence of MAZR. In addition, we observed elevated CD4/CD8 ratios in thymocytes and in peripheral T cells of MAZR-/- mice. Using MHC class I-restricted TCR transgenic mice, we demonstrated that the altered CD4/8 ratio in MAZR-/- mice was, in part, due to redirected differentiation of a fraction of MHC-class I restricted thymocytes into the CD4 lineage. Thus, our data provide genetic evidence that MAZR controls CD8 expression during thymocyte development. In addition, our results may indicate that MAZR is part of the transcription factor network that controls CD4/CD8 cell fate decisions of DP thymocytes. Supported by the Austrian Science Fund (P19930, SFB-F2305 and START Program Y-163).