Alterations of the thymic selection process in transgenic mice expressing SV40 large T antigen

We generated SV40 T antigen transgenic mice (lines SVT125, SVT127, and SVT248) which developed unique thymic carcinomas originating from thymic cortical epithelial cells. In these mice we observed alterations in the thymic selection process not reported before in SV40 T antigen transgenic mice. Along with tumor cell growth, thymocytes increased in number and the proportion of CD4 or CD8 single positive cells rose to 10 times the normal level. Expression of SV40 T antigen was detectable by Northern analysis in thymic stromal cells but not in thymocytes. Thymic stromal cell lines, derived from the thymic tumor, produced high levels of cytokines which caused morphological transformation and growth stimulation in hematopoietic stem cells, including fetal liver cells and bone marrow cells. These observations suggest that the unusual multiplication of thymocytes and the alterations in thymic selection are the result of the activity of thymic stromal cells transformed by SV40 T antigen. The cell lines derived from the tumor can thus be used to study cytokines involved in thymic differentiation of T cells.