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

TLDR

IL‑7 is essential for the effector‑to‑memory transition, yet its potential as an adjuvant has not been explored. In mice immunized against the HY antigen, recombinant IL‑7 and IL‑15 were administered during vaccination, with IL‑7 providing costimulation and IL‑15 enhancing the proliferative burst. IL‑7 and IL‑15 boosted effector responses to both dominant and subdominant antigens, expanded CD8 memory pools that persisted long after cytokine withdrawal, and conferred superior survival against an HY‑expressing tumor, confirming their adjuvant activity.

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.