Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool

Fraia Melchionda, Terry J. Fry, Matthew J. Milliron, Melissa A. McKirdy, Yutaka Tagaya, Crystal L. Mackall

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1177-1187
Number of pages11
JournalJournal of Clinical Investigation
Volume115
Issue number5
DOIs
StatePublished - May 1 2005

ASJC Scopus subject areas

  • Medicine(all)

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    Melchionda, F., Fry, T. J., Milliron, M. J., McKirdy, M. A., Tagaya, Y., & Mackall, C. L. (2005). Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool. Journal of Clinical Investigation, 115(5), 1177-1187. https://doi.org/10.1172/JCI200523134