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 CD4(+)CD25(+)Foxp3(+) 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 γ-rays of WBI. The 2-Gy WBI significantly enhanced the ratios of CD4(+)CD25(+) Treg cells and CD4(+)CD25(+)Foxp3(+) Treg cells to CD4(+) T cells in peripheral blood, lymph nodes, spleens and thymi of mice. The CD4(+)CD25(+) 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 γ-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 CD4(+)CD25(+)Foxp3(+) Treg cells in the periphery of naive or immunized mice. The enhanced proportion of CD4(+)CD25(+)Foxp3(+) Treg cells in the periphery by a low dose of WBI may make hosts more susceptible to immune tolerance induction.
Qu
Yanyan
Y
Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Zhang
Baojun
B
Liu
Shuchun
S
Zhang
Aijun
A
Wu
Tingting
T
Zhao
Yong
Y
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism*; D016827:CD8 Antigens / Q000276:immunology; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism*; D005720:Gamma Rays; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology / Q000528:radiation effects / Q000601:surgery; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D015704:CD4 Antigens; D016827:CD8 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit