Document Detail


Different radiosensitivity of CD4(+)CD25(+) regulatory T cells and effector T cells to low dose gamma irradiation in vitro.
MedLine Citation:
PMID:  20958220     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To determine the radiosensitivity difference of human Cluster of Differentiation (CD)4(+)CD25(+) regulatory T cells (Treg) and effector T cells to low dose gamma ray and elucidate the underlying mechanisms in vitro.
MATERIALS AND METHODS: Blood samples were collected from five health subjects and five patients with advanced hepatocellular carcinoma (HCC). Treg and CD4(+)CD25⁻ T cells were selected using magnetic microbeads. The proliferative profiles, cytokine secretion, and differential expressions of apoptosis-related proteins in Treg and CD4(+)CD25⁻ T cells were compared using [³H]-thymidine incorporation, Luminex assay and flow cytometry when treated with various low doses of γ-ray.
RESULTS: A dose-dependent reduction of proliferation in response to irradiation which paralleled the induction of apoptosis existed in Treg and CD4(+)CD25⁻ T cells. Treg were more radiosensitive to low-dose irradiation (0.94 Gray [Gy]) than effector T cells. The interferon-γ (IFNγ) was significantly upregulated and interleukin 10 (IL-10) was significantly downregulated in irradiated Treg. An enhanced immune response to low dose gamma ray existed in the peripheral blood in patients with advanced HCC. Higher levels of active caspase-3, CD95, B cell lymphoma 2 (Bcl-2)-associated X protein (Bax) expression were observed in Treg compared to CD4(+)CD25⁻ T cells. In addition, gamma irradiation activated CD4(+)CD25⁻ T cells to express CD25.
CONCLUSIONS: These studies revealed that Treg were more radiosensitive than CD4(+)CD25⁻ T cells to low dose irradiation. Higher expressions of apoptosis-related proteins such as caspase-3, CD95 and Bax were observed in Treg when compared to CD4(+)CD25⁻ T cells. Our results suggest that treatment with low doses of gamma irradiation may be a viable strategy to enhance immune response in patients with advanced HCC.
Authors:
Mengde Cao; Roniel Cabrera; Yiling Xu; Chen Liu; David Nelson
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-20
Journal Detail:
Title:  International journal of radiation biology     Volume:  87     ISSN:  1362-3095     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-01-24     Revised Date:  2013-12-19    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  71-80     Citation Subset:  IM; S    
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MeSH Terms
Descriptor/Qualifier:
Aged
Antigens, CD95 / metabolism
Apoptosis / radiation effects
Carcinoma, Hepatocellular / immunology,  pathology,  radiotherapy
Caspase 3 / metabolism
Cell Proliferation / radiation effects
Dose-Response Relationship, Radiation
Female
Gamma Rays / therapeutic use*
Humans
Interferon-gamma / biosynthesis
Interleukin-10 / biosynthesis
Liver Neoplasms / immunology,  pathology,  radiotherapy
Male
Middle Aged
Radiation Tolerance / immunology
T-Lymphocyte Subsets / immunology*,  metabolism,  pathology,  radiation effects*
T-Lymphocytes, Regulatory / immunology*,  metabolism,  pathology,  radiation effects*
bcl-2-Associated X Protein / metabolism
Grant Support
ID/Acronym/Agency:
AI061158/AI/NIAID NIH HHS; DK 60443/DK/NIDDK NIH HHS; R01 AI061158/AI/NIAID NIH HHS; RR00082/RR/NCRR NIH HHS; T32 DK060443/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/BAX protein, human; 0/FAS protein, human; 0/IL10 protein, human; 0/bcl-2-Associated X Protein; 130068-27-8/Interleukin-10; 82115-62-6/Interferon-gamma; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3
Comments/Corrections

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