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

• Published in: International journal of radiation biology Vol. 87; no. 1; pp. 71 - 80
• Main Authors: Cao, Mengde, Cabrera, Roniel, Xu, Yiling, Liu, Chen, Nelson, David
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.01.2011; Taylor & Francis
• Subjects: 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
• DOI: 10.3109/09553002.2010.518208

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.