The effect of ionizing radiation on the homeostasis and functional integrity of murine splenic regulatory T cells

被引:64
作者
Balogh, Andrea [1 ]
Persa, Eszter [1 ]
Bogdandi, Eniko Noemi [1 ]
Benedek, Anett [1 ]
Hegyesi, Hargita [2 ]
Safrany, Geza [2 ]
Lumniczky, Katalin [1 ]
机构
[1] Frederic Joliot Curie Natl Res Inst Radiobiol & R, Div Cellular & Immune Radiobiol, H-1221 Budapest, Hungary
[2] Frederic Joliot Curie Natl Res Inst Radiobiol & R, Div Mol & Tumor Radiobiol, H-1221 Budapest, Hungary
基金
匈牙利科学研究基金会; 英国医学研究理事会;
关键词
Regulatory T cells; Irradiation; Apoptosis; Ki67; CTLA4; MEDIATED REGRESSION; SELF-TOLERANCE; TGF-BETA; TUMOR; IRRADIATION; EXPRESSION; CANCER; IMMUNOTHERAPY; RADIOTHERAPY; ELIMINATION;
D O I
10.1007/s00011-012-0567-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-beta 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.
引用
收藏
页码:201 / 212
页数:12
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