Combined CD137 (4-1BB) and adjuvant therapy generates a developing pool of peptide-specific CD8 memory T cells
Combined CD137 (4-1BB) and adjuvant therapy generates a developing pool of peptide-specific CD8 memory T cells
复制标题
DOI：
10.1093/intimm/dxh371
复制
发表时间：
2006-02-01
影响因子：
4.4
通讯作者：
Vella, AT
中科院分区：
文献类型：
--
作者：
Myers, L;Lee, SW;Vella, AT
在实践中，疫苗应该诱导持久和有效的T细胞免疫，而不促进有害的病理后果。为了达到这个目的，我们用卵清蛋白肽、多肌苷-多胞苷和抗cd137免疫小鼠。接种疫苗的小鼠在淋巴组织和非淋巴组织中保留了大量的功能性CD8 T细胞记忆库。记忆T细胞克隆扩增，产生大量IFN γ，并对水泡性口炎病毒感染产生强烈反应。为了了解疫苗如何发挥作用，我们证明抗原特异性T细胞必须携带CD137才能发生最佳启动。因此，抗cd137激动剂mAb直接刺激肽特异性CD8 T细胞并使其适应生存。相比之下，尽管CD137被抗原呈递细胞表达，CD137缺陷的CD8 T细胞却不能存活。综上所述，这些数据表明CD137和佐剂联合治疗是一种有效的疫苗策略，用于非复制惰性抗原免疫。
In practice, vaccines should induce lasting and efficacious T cell immunity without promoting deleterious pathological consequences. To accomplish this goal we immunized mice with ovalbumin peptide, polyinosinic-polycytidylic and anti-CD137. Vaccinated mice retained a massive functional CD8 T cell memory pool in lymphoid and non-lymphoid tissues for > 1 year. The memory T cells clonally expanded, produced substantial amounts of IFN gamma, and responded vigorously to vesicular stomatitis virus infection. To understand how the vaccine might function, we showed that the antigen-specific T cells must bear CD137 in order for optimal priming to occur. Thus, anti-CD137 agonist mAb directly stimulated peptide-specific CD8 T cells and conditioned them to survive. In contrast, CD137-deficient CD8 T cells did not survive despite CD137 expression by antigen presenting cells. Taken together, the data indicate that CD137 and adjuvant combined therapy is an efficacious vaccine strategy for immunization with non-replicating inert antigen.