Differences in Bcl-2 Expression by T Cell Subsets Alter Their Balance After In Vivo Irradiation to Favor Regulatory NKT Cells and CD4+ CD25+ T Cells in Wild Type But Not p53-/- Mice (141.19)

Abstract

Abstract A more nuanced analysis of the changes in the balance of immune cell subsets is needed to understand the impact of radiation on immune function. We show the balance of T cell subsets changes after increasing single doses of total body irradiation(TBI) or after fractionated irradiation of the lymphoid tissues(TLI) of mice. These changes are due to differences in radioresistance and Bcl-2 expression of the NKT, CD4+CD25+ Treg and conventional T cell subsets to favor CD4+Bcl-2hi NKT and CD4+CD25+Bcl-2hi Treg cells. Reduction of the Bcl-2lo mature T cell subsets was at least 100 fold greater than that of the Bcl-2hi subsets. CD4+ NKT cells upregulated Bcl-2 and developed a Th2 bias after irradiation, while conventional T cells failed to do so. GVHD was more severe after bone marrow transplantation in NKT cell deficient than in wild type hosts and the residual NKT cells were 10 fold more abundant in the wild type spleen after the TLI versus TBI. Although the changes in the balance of T cell subsets and increase in Bcl-2hi cells occurred in irradiated wild type mice, these changes did not occur in p53-/- mice. In conclusion, differences in the level of Bcl-2 and associated differences in resistance of T cell subsets to radiation induced p53 dependent apoptosis results in a marked alteration in the balance of T cell subsets favoring NKT cells and CD4+CD25+ T cells that promote transplantation tolerance.