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

Mengde Cao, Roniel Cabrera, Yiling Xu, Chen Liu, David Nelson

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalInternational Journal of Radiation Biology
Volume87
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Radiation Tolerance
Regulatory T-Lymphocytes
T-Lymphocytes
Hepatocellular Carcinoma
Gamma Rays
Apoptosis
Caspase 3
In Vitro Techniques
bcl-2-Associated X Protein
Proteins
B-Cell Lymphoma
Microspheres
Interleukin-10
Thymidine
Interferons
Flow Cytometry
Down-Regulation
Cytokines
Health

All Science Journal Classification (ASJC) codes

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Keywords

  • apoptosis
  • gamma irradiation
  • hepatocellular carcinoma
  • radiosensitivity
  • regulatory T cells

Cite this

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title = "Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro",
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.",
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Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro. / Cao, Mengde; Cabrera, Roniel; Xu, Yiling; Liu, Chen; Nelson, David.

In: International Journal of Radiation Biology, Vol. 87, No. 1, 01.01.2011, p. 71-80.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro

AU - Cao, Mengde

AU - Cabrera, Roniel

AU - Xu, Yiling

AU - Liu, Chen

AU - Nelson, David

PY - 2011/1/1

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N2 - 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.

AB - 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.

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KW - hepatocellular carcinoma

KW - radiosensitivity

KW - regulatory T cells

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