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《Chinese Journal of Oncology》 2005-12
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Mechanism of augmented anti-tumor immunity in reconstituted lymphopenic mice immunized with melanoma vaccine

MA JUN*, WANG Yi-li, HU Hong-ming, Bernard A Fox, SI Lü-sheng. *The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute for Cancer Research, School of Life Science& Technology, Xi′an Jiaotong University, Xi′an, 710061, China  
Objective To explore mechanisms of the augmented anti-tumor immunity observed in reconstituted lymphopenic mice (RLM) receiving melanoma vaccination. Methods The study is to investigate the anti-tumor immunity of tumor vaccination during early immune reconstitution period following irradiation and cyclophosphamide (CY)-induced lymphopenia. Lymphopenic mice were subsequently reconstituted with nave splenocytes from syngeneic mice and immunized with irradiated melanoma cells F10 (irradiation experiment) and GM-CSF-modified D5 melanoma cells (D5-G6) (CY experiment). Controls included normal C57BL/6 mice receiving the corresponding vaccination, un-immunized nave mice and RLM. 8-10 days after vaccination, tumor vaccine draining lymph nodes (TVDLN) were harvested and phenotyped by FACS analysis. T cells purified from TVDLN were stimulated with anti-CD3 and anti-TCRβ and proliferation was assessed by 3H-TdR incorporation and FACS assay was performed for CD69 expression. Results The augmented anti-tumor immunity correlated with a significant increase in the percentage of T cells with activation/memory phenotype in the TVDLN of vaccinated RLM, compared to that of the controls. There was also a significant increase in the density of DCs in TVDLNs. The activation threshold of T cells generated from vaccinated RLM was significantly decreased, resulting in markedly enhanced proliferating capability upon anti-CD3 stimulation. Conclusion This study suggests that the augmented anti-tumor immunity observed in vaccinated RLM is due to down regulated activation threshold of T cells during lymphopenia-driven T cell proliferation, which may in turn facilitate the breaking down of immune tolerance to weak tumor antigens upon vaccination with tumor cell vaccines.
【Fund】: 国家自然科学基金资助项目(30370549)
【CateGory Index】: R73-3
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