The effect of ionizing radiation on the homeostasis and functional integrity of murine splenic regulatory T cells
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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.
C57Bl/6 mice were irradiated with 2 Gy and alterations in splenic lymphocyte fractions analyzed at different intervals.
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.
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.
KeywordsRegulatory T cells Irradiation Apoptosis Ki67 CTLA4
The authors wish to thank Dr. Serge Candeias for the careful reading of the manuscript and for helpful suggestions in manuscript writing. The authors thank the expert technical assistance of Ms. Erzsébet Fekete. This work was supported by the following grants: European Union FP6-036465/2006 (NOTE), European Union FP7- CEREBRAD-295552/2011 and Hungarian OTKA (Hungarian Scientific Research Fund) K77766 and ETT (Medical Research Council) 827-1/2009.
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