Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Huntington, N.D. et al.

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

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

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.[1]

References

IL-15 transpresentation promotes both human T-cell reconstitution and T-cell-dependent antibody responses in vivo. Huntington, N.D., Alves, N.L., Legrand, N., Lim, A., Strick-Marchand, H., Mention, J.J., Plet, A., Weijer, K., Jacques, Y., Becker, P.D., Guzman, C., Soussan, P., Kremsdorf, D., Spits, H., Di Santo, J.P. Proc. Natl. Acad. Sci. U.S.A. (2011) [Pubmed]

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