Activated CD4+T cells enhance radiation effect through the cooperation of interferon-γ and TNF-α

BMC Cancer

Research Article

Hung T Khong¹  Yixiang Wang²  Soroosh Radfar³ 

[1] Mitchell Cancer Institute, University of South Alabama, 36604-1405, Mobile, Alabama, USA;Mitchell Cancer Institute, University of South Alabama, 36604-1405, Mobile, Alabama, USA;Research Laboratory of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, 100081, Beijing, P.R. China;Mitchell Cancer Institute, University of South Alabama, 36604-1405, Mobile, Alabama, USA;Yale University School of Medicine, Department of Internal Medicine, Hematology Section, P.O. Box 208021, 333 Cedar Street, 06520-8021, New Haven, Connecticut, USA;

关键词: Hela Cell;    Cell Growth Inhibition;    Irradiation Group;    Cervical Cancer Cell Line;    LN229 Cell;   

DOI  :  10.1186/1471-2407-10-60

 received in 2009-11-09, accepted in 2010-02-23,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundApproaches that enhance radiation effect may lead to improved clinical outcome and decrease toxicity. Here we investigated whether activated CD4+ T cells (aCD4) can serve as an effective radiosensitizer.MethodsCD4+ T cells were activated with anti-CD3 and anti-CD28 mAbs. Hela cells were presensitized with aCD4 or conditioned supernatant (aCD4S) or recombinant cytokines for 2 days, followed γ-irradiation. The treated cells were cultured for an additional 2 to 5 days for cell proliferation, cell cycle, and western blot assays. For confirmation, other cancer cell lines were also used.ResultsPresensitization of tumor cells with aCD4 greatly increased tumor cell growth inhibition. Soluble factors secreted from activated CD4+ T cells were primarily responsible for the observed effect. IFN-γ seemed to play a major role. TNF-α, though inactive by itself, significantly augmented the radiosensitizing activity of IFN-γ. aCD4S, but not IFN-γ or IFN-γ/TNF-α combination, was found to enhance the γ-irradiation-induced G2/M phase arrest. Bax expression was highly upregulated in Hela cells presensitized with aCD4S followed by γ-irradiation. The radio-sensitizing activity of aCD4 is not uniquely observed with Hela cell line, but also seen with other cancer cell lines of various histology.ConclusionsOur findings suggest possible molecular and cellular mechanisms that may help explain the radio-sensitization effect of activated lymphocytes, and may provide an improved strategy in the treatment of cancer with radiotherapy.

【 授权许可】

Unknown   
© Wang et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.