T-cell development in mice expressing a cyclin dl transgene in thymic epithelial cells

Cyclin D1 functions to regulate the cell cycle by promoting the transition from G1 into S phase. Transgenic mice were generated that express a cyclin Dl transgene under the control of a keratin 5 promoter. Although the rate of epidermal proliferation increased, minimal hyperplasia of the skin was observed. The predominant phenotypic aberration was a dramatic hyperplasia of the thymus that became overtly apparent by 3 wks of age. Subsequently, the transgenic thymuses continued to increase in size and by 8 wks contained up to 3il09 cells. There was no evidence of lymphomagenesîs. Although peripheral lymphoid organs were also enlarged, the degree of hyperplasia was not as extensive as that observed in the thymus. The hyperplastic thymuses contained well differentiated cortical and medullary regions. By 4 wks there was a 2X increase in the percentage of CD4^-8^- thymocytes compared to age-matched controls and an increased fraction of proliferating cells in this precursor compartment. The relative percentage of CD4⁺8⁺ double positive (DP) cells was somewhat reduced, whereas the single positive (SP) subsets showed a corresponding increase. Although these data suggest enhanced positive selection, there was no significant increase in the fraction of DP or SP cells expressing high levels of CD3 or CD69 in the D1 transgenics. However, both SP subsets contained a greater percentage of proliferating cells than observed in aee matched controls. Studies are underway to define the influence of cyclin D1 transgenic thymic epithelial cells on T-cell development.