2-Gy whole-body irradiation significantly alters the balance of CD4^(+)CD25^(-) T effector cells and CD4^(+)CD25^(+)Foxp3^(+) T regulatory cells in mice

CD4^(+)CD25^(+) T regulatory(Treg)cells are critical in inducing and maintaining immunological self-tolerance as well as transplant tolerance.The effect of low doses of whole-body irradiation(WBI)on CD41CD251Foxp31 Treg cells has not been determined.The proportion,phenotypes and function of CD4^(+)CD25^(+) Treg cells were investigated 0.5,5 and 15 days after euthymic,thymectomized or allogeneic bone marrow transplanted C57BL/6 mice received 2-Gy c-rays of WBI.The 2-Gy WBI significantly enhanced the ratios of CD41CD251 Treg cells and CD4^(+)CD25^(+)Foxp3^(+) Treg cells to CD41 T cells in peripheral blood,lymph nodes,spleens and thymi of mice.The CD41CD251 Treg cells of the WBI-treated mice showed immunosuppressive activities on the immune response of CD4^(+)CD25^(+) T effector cells to alloantigens or mitogens as efficiently as the control mice.Furthermore,2-Gy c-ray WBI significantly increased the percentage of CD4^(+)CD25^(+)Foxp3^(+) Treg cells in the periphery of either thymectomized mice or allogeneic bone marrow transplanted mice.The in vitro assay showed that ionizing irradiation induced less cell death in CD4^(+)CD25^(+)Foxp3^(+) Treg cells than in CD4^(+)CD25^(+) T cells.Thus,a low dose of WBI could significantly enhance the level of functional CD41CD251Foxp31 Treg cells in the periphery of naive or immunized mice.The enhanced proportion of CD41CD251Foxp31 Treg cells in the periphery by a low dose of WBI may make hosts more susceptible to immune tolerance induction.

Roles of FOXP3 in experimental atherosclerosis of ApoE-knockout mice

Background Subtypes of T cells, called regulatory T cells （Treg cell）, play a critical role in limiting autoimmune processes and inflammatory responses, The aim of this study was to explore functional roles of FOXP3 in the manifestation of atherosclerosis in Apolipoprotein E deficient （ApoE）-/- mice. Methods Lentivirus-mediated （siRNA） was used to knock down FOXP3 and FOXP3high＋CD4＋ CD25＋ T cells adoptive transfer assays in high fat diet ApoE-/- mice were done. The resulting atherosclerotie lesions were assessed by determining FOXP3 transcript levels and investigating the expression of FOXP3 protein in different tissues. Results Animals treated with siRNA of FOXP3 showed a significant increase in atherosclerotic lesion formation and a reduction in the number of FOXP3＋CD4＋CD25＋ T cells compared with other groups. Transfer of FOXP3highCD4＋CD25＋ T cells significantly decreased atherosclerotic plaque formation and increased the number of FOXP3＋ CD4＋ CD25＋ T cells. FOXP3 protein levels and FOXP3 transcript levels were lowest in the siRNA group, and were highest in tissues from the Treg transfer group. Conclusion FOXP3 plays an important role in regulating the inflammatory response within the atherosclerotic lesion. It can inhibit significantly the progression of the atherosclerosis plaque in ApoE-/- mice.