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

Inflamm Res. 2013 Feb;62(2):201-12. doi: 10.1007/s00011-012-0567-y. Epub 2012 Oct 19.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / radiation effects*
  • Cell Proliferation / radiation effects
  • Homeostasis
  • Interleukin-10 / genetics
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Radiation, Ionizing*
  • Spleen / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / radiation effects*
  • Transforming Growth Factor beta / genetics


  • RNA, Messenger
  • Transforming Growth Factor beta
  • Interleukin-10