Abstract
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.
Acknowledgements
This work was supported by National Institutes of Health grant AI061158, DK 60443 and GCRC Grant (RR00082) (to D.N.).
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.