The effect of ionizing radiation on the homeostasis and functional integrity of murine splenic regulatory T cells.
OBJECTIVE
Radiotherapy affects antitumor immune responses; therefore, it is important to study radiation effects on various compartments of the immune system. Here we report radiation effects on the homeostasis and function of regulatory T (Treg) cells, which are important in down-regulating antitumor immune responses.


METHODS
C57Bl/6 mice were irradiated with 2 Gy and alterations in splenic lymphocyte fractions analyzed at different intervals.


RESULTS
Total CD4+ numbers showed stronger decrease after irradiation than CD4+Foxp3+ Tregs. Tregs were less prone to radiation-induced apoptosis than CD4+Foxp3- T cells. The ratio of CD4+Foxp3- and CD4+Foxp3+ fractions within the proliferating CD4+ pool progressively changed from 74:26 in control animals to 59:41 eleven days after irradiation, demonstrating a more dynamic increase in the proliferation and regeneration of the Treg pool. The CD4+Foxp3+ fraction expressing cell-surface CTLA4, an antigen associated with Treg cell activation increased from 5.3 % in unirradiated mice to 10.5 % three days after irradiation. The expression of IL-10 mRNA was moderately upregulated, while TGF-β expression was not affected. On the other hand, irradiation reduced Treg capacity to suppress effector T cell proliferation by 2.5-fold.


CONCLUSIONS
Tregs are more radioresistant, less prone to radiation-induced apoptosis, and have faster repopulation kinetics than CD4+Foxp3- cells, but irradiated Tregs are functionally compromised, having a reduced suppressive capacity.
Division of Cellular and Immune Radiobiology, Frédéric Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Anna u. 5, Budapest 1221, Hungary.
Andrea
A
Balogh
Eszter
E
Persa
Enikő Noémi
EN
Bogdándi
Anett
A
Benedek
Hargita
H
Hegyesi
Géza
G
Sáfrány
Katalin
K
Lumniczky
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D006706:Homeostasis; D016753:Interleukin-10 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000528:radiation effects*; D016212:Transforming Growth Factor beta / Q000235:genetics
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10