In vivo expansion, persistence, and function of peptide vaccine-induced CD8 T cells occur independently of CD4 T cells.
In vivo expansion, persistence, and function of peptide vaccine-induced CD8 T cells occur independently of CD4 T cells.
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DOI：
10.1158/0008-5472.can-08-3134
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发表时间：
2008-12-01
期刊：
影响因子：
11.2
通讯作者：
Celis E
中科院分区：
文献类型：
--
作者：
Assudani D;Cho HI;DeVito N;Bradley N;Celis E
目前正在致力于开发有效的癌症治疗性疫苗。具体地说，特性良好的亚单位疫苗，旨在产生抗肿瘤细胞毒性CD8 T细胞反应。由于CD4T细胞参与CD8T细胞应答的不同阶段，因此研究CD4T细胞在这些疫苗诱导和维持抗肿瘤CD8T细胞应答中的作用具有重要意义。最近的证据表明，CD4T细胞需要记忆CD8T细胞的长期存在，在癌症免疫治疗的情况下，这将是防止肿瘤复发的关键。本研究的目的是评估亚基(多肽或DNA)疫苗诱导的抗原特异性CD8T细胞的产生和维持是否需要CD4T细胞。我们使用了一种疫苗策略，将代表CD8T细胞表位的合成肽、共刺激的抗CD40抗体和Toll样受体激动剂(TriVax)相结合，以产生大量抗原特异性的CD8T细胞反应。我们的结果表明，在TriVax产生的整个免疫反应中，抗原特异性CD8T细胞的下降速度(克隆性收缩)及其功能状态不受CD4T细胞的存在或不存在的影响。我们认为，这些结果对设计有效的癌症疫苗接种策略具有重要意义。
Significant efforts are being devoted towards the development of effective therapeutic vaccines against cancer. Specifically, well-characterized subunit vaccines, which are designed to generate anti-tumor cytotoxic CD8 T cell responses. Since CD4 T cells participate at various stages of CD8 T cell responses, it is important to study the role of CD4 T cells in the induction and persistence of anti-tumor CD8 T cell responses by these vaccines. Recent evidence points to the requirement of CD4 T cells for the long-term persistence of memory CD8 T cells, which in the case of cancer immunotherapy would be critical for the prevention of tumor recurrences. The purpose of the present study was to assess whether CD4 T cells are necessary for the generation and maintenance of antigen-specific CD8 T cells induced by subunit (peptide or DNA) vaccines. We have utilized a vaccination strategy that combines synthetic peptides representing CD8 T cell epitopes, a costimulatory anti-CD40 antibody and a Toll-like receptor agonist (TriVax) to generate large numbers of antigen-specific CD8 T cell responses. Our results show that the rate of decline (clonal contraction) of the antigen-specific CD8 T cells and their functional state is not affected by the presence or absence of CD4 T cells throughout the immune response generated by TriVax. We believe that these results bear importance for the design of effective vaccination strategies against cancer.