Myers Lara, Lee Seung Woo, Rossi Robert J, Lefrancois Leo, Kwon Byoung S, Mittler Robert S, Croft Michael, Vella Anthony T
Department of Immunology, School of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
Int Immunol. 2006 Feb;18(2):325-33. doi: 10.1093/intimm/dxh371. Epub 2005 Dec 22.
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 IFNgamma, 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.
在实际应用中，疫苗应诱导持久且有效的T细胞免疫，同时不引发有害的病理后果。为实现这一目标，我们用卵清蛋白肽、聚肌苷酸-聚胞苷酸和抗CD137对小鼠进行免疫。接种疫苗的小鼠在淋巴组织和非淋巴组织中保留了大量功能性CD8 T细胞记忆库超过1年。记忆T细胞发生克隆性扩增，产生大量干扰素γ，并对水疱性口炎病毒感染产生强烈反应。为了解该疫苗的作用机制，我们发现抗原特异性T细胞必须表达CD137才能实现最佳的启动。因此，抗CD137激动剂单克隆抗体直接刺激肽特异性CD8 T细胞并使其存活。相比之下，尽管抗原呈递细胞表达CD137，但缺乏CD137的CD8 T细胞仍无法存活。综上所述，数据表明CD137与佐剂联合疗法是一种用于非复制性惰性抗原免疫的有效疫苗策略。
