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

Andrea Balogh, Eszter Persa, Eniko Noémi Bogdándi, Anett Benedek, Hargita Hegyesi, Géza Sáfrány, Katalin Lumniczky

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)201-212
Number of pages12
JournalInflammation Research
Volume62
Issue number2
DOIs
Publication statusPublished - Feb 1 2013

    Fingerprint

Keywords

  • Apoptosis
  • CTLA4
  • Irradiation
  • Ki67
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this