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.
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.
Authors: Abdiaziz S Mohamood; Crystal J Trujillo; Dongfeng Zheng; Chunfa Jie; Francisco Martinez Murillo; Jonathan P Schneck; Abdel Rahim A Hamad Journal: Int Immunol Date: 2006-06-12 Impact factor: 4.823
Authors: Carmen Timke; Hubertus Schmitz Winnenthal; Felix Klug; Falk F F Roeder; Andreas Bonertz; Christoph Reissfelder; Nathalie Rochet; Moritz Koch; Christine Tjaden; Markus W Buechler; Juergen Debus; Jens Werner; Philipp Beckhove; Jürgen Weitz; Peter E Huber Journal: BMC Cancer Date: 2011-04-13 Impact factor: 4.430
Authors: Shelby Lennon; Ayman Oweida; Dallin Milner; Andy V Phan; Shilpa Bhatia; Benjamin Van Court; Laurel Darragh; Adam C Mueller; David Raben; Jorge L Martínez-Torrecuadrada; Todd M Pitts; Hilary Somerset; Kimberly R Jordan; Kirk C Hansen; Jason Williams; Wells A Messersmith; Richard D Schulick; Philip Owens; Karyn A Goodman; Sana D Karam Journal: Clin Cancer Res Date: 2019-04-03 Impact factor: 12.531
Authors: Jonathan E Schoenhals; Steven N Seyedin; Clark Anderson; Eric D Brooks; Yun R Li; Ahmed I Younes; Sharareh Niknam; Ailin Li; Hampartsoum B Barsoumian; Maria Angelica Cortez; James W Welsh Journal: Transl Lung Cancer Res Date: 2017-04
Authors: Ravi B Patel; Claire C Baniel; Raghava N Sriramaneni; Kristin Bradley; Stephanie Markovina; Zachary S Morris Journal: Brachytherapy Date: 2018-08-02 Impact factor: 2.362
Authors: Ayman J Oweida; Adam C Mueller; Miles Piper; Dallin Milner; Benjamin Van Court; Shilpa Bhatia; Andy Phan; Thomas Bickett; Kimberly Jordan; Theresa Proia; Richard Schulick; Wells A Messersmith; Marco Del Chiaro; Eric Clambey; Michael J Gough; Jason Williams; Kirk Hansen; Karyn Goodman; Sana D Karam Journal: Cancer Immunol Immunother Date: 2020-10-23 Impact factor: 6.968