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© Research
Publication : Proceedings of the National Academy of Sciences of the United States of America

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 28 Mar 2011

Huntington ND, Alves NL, Legrand N, Lim A, Strick-Marchand H, Mention JJ, Plet A, Weijer K, Jacques Y, Becker PD, Guzman C, Soussan P, Kremsdorf D, Spits H, Di Santo JP

Link to Pubmed [PMID] – 21444793

Proc. Natl. Acad. Sci. U.S.A. 2011 Apr;108(15):6217-22

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.

http://www.ncbi.nlm.nih.gov/pubmed/21444793