A novel T cell-based vaccine capable of stimulating long-term functional CTL memory against B 16 melanoma via CD40L signaling
A novel T cell-based vaccine capable of stimulating long-term functional CTL memory against B 16 melanoma via CD40L signaling作者机构：Saskatchewan Cancer Agency Department of Oncology University of Saskatchewan Saskatoon Saskatchewan Canada Department of Pathology University ofSaskatchewan Saskatoon Saskatchewan Canada and Department of Epidemiology and Community Medicine University of Ottawa Ottawa Ont. Canada Xie and Wang contributed equally to this study.
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2013年第10卷第1期
页 面：72-77页
核心收录：
学科分类：071011[理学-生物物理学] 0710[理学-生物学] 02[经济学] 0202[经济学-应用经济学] 020208[经济学-统计学] 07[理学] 0714[理学-统计学（可授理学、经济学学位）] 070103[理学-概率论与数理统计] 0701[理学-数学]
基 金：the Canadian Institutes of Health Research Canadian Breast Cancer Foundation Postdoctoral Fellowships from the Saskatchewan Health Research Foundation the Scholarship Council of Chinese Education Ministry
主 题：antitumor immunity CD4OL memory CTL T cell-based vaccine
摘 要：The ultimate goal of antitumor vaccines is to develop memory CD8＋ cytotoxic T lymphocytes （CTLs）, which are critical mediators of antitumor immunity. We previously demonstrated that the ovalbumin （OVA）-specific CD4＋ T cell-based （OVA-TExo） vaccine generated using OVA-pulsed dendritic cell （DCovA）-released exosomes （EXOovA） stimulate CTL responses via IL-2 and costimulatory CD80 signaling. To assess the potential involvement of other costimulatory pathways and to define the key constituent of costimulation for memory CTL development, we first immunized wild-type （WT） C57BIJ6 and gene-knockout mice with WT CD4~ OVA-TExo cells or OVA-TExo cells with various molecular deficiencies. We then assessed OVA-specific primary and recall CTL responses using PE-H-2Kb/ 0VA257_264 tetramer and FITC-anti-CD8 antibody staining by flow cytometry. We also examined antitumor immunity against the OVA-expressing B16 melanoma cell line BL6-1OovA. We demonstrated that CD4＋ OVA-TExo cells stimulated more efficient CTL responses compared to DCovA. By assessing primary and recall CTL responses in mice immunized with OVA-TExo or with OVA-TExo lacking the costimulatory molecules CD4OL, 4-1BBL or OX4OL, we demonstrated that these costimulatory signals are dispensable for CTL priming by OVA-TExo. Interestingly, CD4OL, but not 4-1BBL or OX4OL, plays a crucial role in the development of functional memory CTLs against BL6-1OovA tumors. Overall, this work suggests that a novel CD4＋ T cell-based vaccine that is capable of stimulating long-term functional CTL memory via CD40L signaling may represent a novel, efficient approach to antitumor vaccination.
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