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/jci23134
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发表时间：
2005-05
期刊：
影响因子：
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通讯作者：
F. Melchionda;T. Fry;Matthew Milliron;Melissa A McKirdy;Y. Tagaya;C. Mackall
中科院分区：
文献类型：
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作者：
F. Melchionda;T. Fry;Matthew Milliron;Melissa A McKirdy;Y. Tagaya;C. Mackall
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-mediated 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.
