IL-15 transpresentation promotes both human T-cell reconstitution and T-cell-dependent antibody responses in vivo

Nicholas D. Huntington, Nuno L. Alves, Nicolas Legrand, Annick Lim, Helene Strick-Marchand, Jean Jacques Mention, Ariane Pletf, Kees Weijer, Yannick Jacques, Pablo D. Becker, Carlos Guzman, Patrick Soussan, Dina Kremsdorf, Hergen Spits, James P. Di Santo

Research output: Contribution to journalArticleResearchpeer-review

67 Citations (Scopus)

Abstract

Cytokine immunotherapies targeting T lymphocytes are attractive clinical interventions against viruses and tumors. In the mouse, the homeostasis of memory α/β CD8+ T cells and natural killer (NK) cells is significantly improved with increased IL-15 bioavailability. In contrast, the role of "transpresented" IL-15 on human T-cell development and homeostasis in vivo is unknown. We found that both CD8 and CD4 T cells in human immune system (HIS) mice are highly sensitive to transpresented IL-15 in vivo, with both naïve (CD62L+CD45RA+) and memory phenotype (CD62L?CD45RO+) subsets being significantly increased following IL-15 "boosting." The unexpected global improvement in human T-cell homeostasis involved enhanced proliferation and survival of both naïve and memory phenotype peripheral T cells, which potentiated B-cell responses by increasing the frequency of antigen-specific responses following immunization. Transpresented IL-15 did not modify T-cell activation patterns or alter the global T-cell receptor (TCR) repertoire diversity. Our results indicate an unexpected effect of IL-15 on human T cells in vivo, in particular on CD4+ T cells. As IL-15 promotes human peripheral T-cell homeostasis and increases the frequency of neutralizing antibody responses in HIS mice, IL-15 immunotherapy could be envisaged as a unique approach to improve vaccine responses in the clinical setting.

Original languageEnglish
Pages (from-to)6217-6222
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number15
DOIs
Publication statusPublished - 12 Apr 2011
Externally publishedYes

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