Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool
Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool
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DOI：
10.1172/jci200523134
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发表时间：
2005-05-01
影响因子：
15.9
通讯作者：
Mackall, CL
中科院分区：
文献类型：
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作者：
Melchionda, F;Fry, TJ;Mackall, CL
目前的T细胞记忆模型暗示了IL-7在效应器到记忆转换中的关键作用，提高了IL-7治疗可能增强疫苗应答的可能性。据我们所知，在此之前尚未研究IL-7的佐剂活性。我们在针对雄性抗原HY的免疫过程中向小鼠施用重组人IL-7（rhIL-7），并将这些结果与用rhIL-2和rhIL-15免疫的小鼠获得的结果进行比较。给予rhIL-7或rhIL- 15，而不是rhIL-2，增加了针对这些显性抗原的效应细胞，并显着增强了CD 8（+）效应子亚显性抗原。细胞因子增强效应库产生的机制是多因素的，包括rhIL-7介导的共刺激和rhIL-15介导的增殖爆发增强。在马槟榔碱处理的小鼠中，抗原特异性反应的收缩期被夸大;然而，rhIL-7或rhIL-15处理组中的CD 8（+）记忆池显示出上级长期存活率，导致在细胞因子停止后很长时间内保持定量优势，如在细胞因子停止后数周用表达HY的肿瘤激发后存活率改善所示。这些结果证实了rhIL-15的佐剂活性，并证明rhIL-7也可作为有效的疫苗佐剂，通过增强对亚显性抗原的应答和改善CD 8（+）T细胞记忆库的存活来扩大免疫力。
Current models of T cell memory implicate a critical role for IL-7 in the effector-to-memory transition, raising the possibility that IL-7 therapy might enhance vaccine responses. IL-7 has not been studied, to our knowledge, before now for adjuvant activity. We administered recombinant human IL-7 (rhIL-7) to mice during immunization against the male antigen HY and compared these results with those obtained from mice immunized with rhIL-2 and rhIL-15. Administration of rhIL-7 or rhIL- 15, but not rhIL-2, increased effector cells directed against these dominant antigens and dramatically enhanced CD8(+) effectors to subdominant antigens. The mechanisms by which the cytokines augmented effector pool generation were multifactorial and included rhIL-7-mediated costimulation and rhIL-15-mecliated augmentation of the proliferative burst. The contraction phase of the antigen-specific response was exaggerated in cytokine-treated mice; however, CD8(+) memory pools in rhIL-7- or rhIL-15-treated groups demonstrated superior long-term survival resulting in quantitative advantages that remained long after the cytokines were discontinued, as demonstrated by improved survival after challenge with an HY-expressing tumor undertaken several weeks after cytokine cessation. These results confirm the adjuvant activity of rhIL-15 and demonstrate that rhIL-7 also serves as a potent vaccine adjuvant that broadens immunity by augmenting responses to subdominant antigens and improving the survival of the CD8(+) T cell memory pool.