Sandra Beer‐Hammer

The lymphocyte‐specific adapter protein SLy1 has previously been identified as indispensable for thymocyte development and T‐cell proliferation and, recently, as a cause of X‐linked combined immunodeficiency in humans that recapitulates many of the abnormalities reported in SLy1 KO and SLy1 d/d mice. As SLy1 KO NK cells show increased levels of p53, we focused our research on the interdependency of SLy1 and p53 for thymocyte development. Using RT‐PCR and immunoblot analysis, we observed increased levels of p53 as well as DNA damage response proteins in SLy1 KO thymocytes. To test for rescue from SLy1‐induced deficiencies in thymocyte development like reduced thymocyte numbers and reduced DN to DP progression, we generated a mouse model with T cell‐specific p53‐deficiency on an SLy1 KO background and analyzed lymphocyte populations in these mice and respective controls. Astonishingly, SLy1 KO ‐typical deficiencies were retained, showing that SLy1 is mechanistically independent of p53. Studies of apoptosis and proliferation in SLy1KO thymocytes revealed decreased proliferation in the DN3 subpopulation as a possible reason for the decreased thymocyte number. In mice with p53‐deficient T cells, we observed tumor formation leading to reduced survival, preferentially in SLy1 WT mice. Thus, we suggest that a SLy1‐deficiency reduces proliferation, resulting in less hematologic tumors initiated by the p53‐deficiency.