Programming for CD8 T cell memory development requires IL-12 or type I IFN.

Programming for CD8 T cell memory development requires IL-12 or type I IFN.
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DOI:
10.4049/jimmunol.0803484
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发表时间:
2009-03-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Mescher MF
Mescher MF
中科院分区:
其他
文献类型:
--
作者:
Xiao Z;Casey KA;Jameson SC;Curtsinger JM;Mescher MF

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炎症可以对CD8 T细胞记忆的发展产生积极和消极的影响,但相关细胞因子的相对贡献和细胞靶点尚不清楚。使用缺乏IL-12、I型IFN或两者受体的CD8 T细胞,我们发现这些细胞因子直接作用于CD8 T细胞,以支持对牛痘病毒和单核增生李斯特菌感染的记忆形成。对牛痘的记忆主要由IL-12支持,而IL-12和I型IFN都有助于对李斯特菌的记忆形成。与记忆形成相反,无法对IL-12或I型IFN产生反应对原发性扩张水平的影响相对较小,在李斯特菌反应的情况下最多减少3倍。我们进一步表明,IL-12的记忆发育编程在naïve CD8 T细胞对Ag的初始反应后三天内完成。这种编程不会导致表达杀伤细胞凝集素样受体G1 (KLRG1)的群体的形成,并且大多数产生的记忆细胞具有中央记忆细胞的CD62Lhi表型特征。与此一致的是,细胞在再次受到攻击时经历强烈的扩张,并提供保护性免疫。这些数据表明,IL-12和I型IFN在确定初始CD8 T细胞遭遇Ag是否导致保护性记忆群体形成方面起着至关重要的早期作用。
Inflammation can have both positive and negative effects on development of CD8 T cell memory, but the relative contributions and cellular targets of the cytokines involved are unclear. Using CD8 T cells lacking receptors for IL-12, Type I IFN, or both, we show that these cytokines act directly on CD8 T cells to support memory formation in response to vaccinia virus and Listeria monocytogenes infections. Development of memory to vaccinia is supported predominantly by IL-12, while both IL-12 and Type I IFN contribute to memory formation in response to Listeria. In contrast to memory formation, the inability to respond to IL-12 or Type I IFN had a relatively small impact on the level of primary expansion, with at most a 3-fold reduction in the case of responses to Listeria. We further show that programming for memory development by IL-12 is complete within three days of the initial naïve CD8 T cell response to Ag. This programming does not result in formation of a population that expresses killer cell lectin-like receptor G1 (KLRG1), and the majority of the resulting memory cells have a CD62Lhi phenotype characteristic of central memory cells. Consistent with this, the cells undergo strong expansion upon re-challenge and provide protective immunity. These data demonstrate that IL-12 and Type I IFN play an essential early role in determining whether Ag encounter by naive CD8 T cells results in formation of a protective memory population.
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