Abstract:
The molecular mechanisms leading to the establishment of immunological memory are inadequately understood, limiting the development of effective vaccines and durable antitumor immune therapies. Here, we show that ectopic OCA-B expression is sufficient to improve antiviral memory recall responses, while having minimal effects on primary effector responses. At peak viral response, short-lived effector T cell populations are expanded but show increased Gadd45b and Socs2 expression, while memory precursor effector cells show increased expression of Bcl2, Il7r, and Tcf7 on a per-cell basis. Using an OCA-B mCherry reporter mouse line, we observe high OCA-B expression in CD4+ central memory T cells. We show that early in viral infection, endogenously elevated OCA-B expression prospectively identifies memory precursor cells with increased survival capability and memory recall potential. Cumulatively, the results demonstrate that OCA-B is both necessary and sufficient to promote CD4 T cell memory in vivo and can be used to prospectively identify memory precursor cells.
摘要:
导致建立免疫记忆的分子机制还没有被充分理解,限制开发有效的疫苗和持久的抗肿瘤免疫疗法。这里,我们表明异位OCA-B表达足以改善抗病毒记忆回忆反应,而对主要效应反应的影响最小。在病毒反应高峰期,短寿命效应T细胞群体扩大,但显示增加的Gadd45b和Socs2表达,而记忆前体效应细胞显示Bcl2、Il7r、和Tcf7在每个细胞的基础上。使用OCA-BmCherry记者鼠标线,我们观察到CD4+中枢记忆T细胞中OCA-B的高表达。我们表明,在病毒感染的早期,内源性升高的OCA-B表达前瞻性地鉴定了具有增加的生存能力和记忆回忆潜力的记忆前体细胞。累计,结果证明OCA-B对于体内促进CD4T细胞记忆是必需和充分的,并且可用于前瞻性地鉴定记忆前体细胞.