title: IL-15 transpresentation promotes both human T-cell reconstitution and T-cell-dependent antibody responses in vivo.
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.
authors: Innate Immunity Unit, Immunology Department, Institut Pasteur, 75724 Paris, France. nhunting@pasteur.fr
authors: Nicholas D
authors: ND
authors: Huntington
authors: Nuno L
authors: NL
authors: Alves
authors: Nicolas
authors: N
authors: Legrand
authors: Annick
authors: A
authors: Lim
authors: Helene
authors: H
authors: Strick-Marchand
authors: Jean-Jacques
authors: JJ
authors: Mention
authors: Ariane
authors: A
authors: Plet
authors: Kees
authors: K
authors: Weijer
authors: Yannick
authors: Y
authors: Jacques
authors: Pablo D
authors: PD
authors: Becker
authors: Carlos
authors: C
authors: Guzman
authors: Patrick
authors: P
authors: Soussan
authors: Dina
authors: D
authors: Kremsdorf
authors: Hergen
authors: H
authors: Spits
authors: James P
authors: JP
authors: Di Santo
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D053647:Receptors, Interleukin-15 / Q000037:antagonists & inhibitors
chemical_list: D019409:Interleukin-15; D016693:Receptors, Antigen, T-Cell, alpha-beta; D053647:Receptors, Interleukin-15