Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro

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 a...

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Vydáno v:	International journal of radiation biology Ročník 87; číslo 1; s. 71 - 80
Hlavní autoři:	Cao, Mengde, Cabrera, Roniel, Xu, Yiling, Liu, Chen, Nelson, David
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Informa Healthcare 01.01.2011 Taylor & Francis
Témata:	Aged apoptosis Apoptosis - radiation effects bcl-2-Associated X Protein - metabolism Carcinoma, Hepatocellular - immunology Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - radiotherapy Caspase 3 - metabolism Cell Proliferation - radiation effects Dose-Response Relationship, Radiation fas Receptor - metabolism Female gamma irradiation Gamma Rays - therapeutic use hepatocellular carcinoma Humans In Vitro Techniques Interferon-gamma - biosynthesis Interleukin-10 - biosynthesis Liver Neoplasms - immunology Liver Neoplasms - pathology Liver Neoplasms - radiotherapy Male Middle Aged Radiation Tolerance - immunology radiosensitivity regulatory T cells T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocyte Subsets - pathology T-Lymphocyte Subsets - radiation effects T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism T-Lymphocytes, Regulatory - pathology T-Lymphocytes, Regulatory - radiation effects
ISSN:	0955-3002, 1362-3095, 1362-3095
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0955-3002 1362-3095 1362-3095
DOI:	10.3109/09553002.2010.518208