title: IL-10 promotes homeostatic proliferation of human CD8(+) memory T cells and, when produced by CD1c(+) DCs, shapes naive CD8(+) T-cell priming.
abstract: IL-10 is an anti-inflammatory cytokine that inhibits maturation and cytokine production of dendritic cells (DCs). Although mature DCs have the unique capacity to prime CD8(+) CTL, IL-10 can promote CTL responses. To understand these paradoxic findings, we analyzed the role of IL-10 produced by human APC subsets in T-cell responses. IL-10 production was restricted to CD1c(+) DCs and CD14(+) monocytes. Interestingly, it was differentially regulated, since R848 induced IL-10 in DCs, but inhibited IL-10 in monocytes. Autocrine IL-10 had only a weak inhibitory effect on DC maturation, cytokine production, and CTL priming with high-affinity peptides. Nevertheless, it completely blocked cross-priming and priming with low-affinity peptides of a self/tumor-antigen. IL-10 also inhibited CD1c(+) DC-induced CD4(+) T-cell priming and enhanced Foxp3 induction, but was insufficient to induce T-cell IL-10 production. CD1c(+) DC-derived IL-10 had also no effect on DC-induced secondary expansions of memory CTL. However, IL-15-driven, TCR-independent proliferation of memory CTL was enhanced by IL-10. We conclude that DC-derived IL-10 selects high-affinity CTL upon priming. Moreover, IL-10 preserves established CTL memory by enhancing IL-15-dependent homeostatic proliferation. These combined effects on CTL priming and memory maintenance provide a plausible mechanism how IL-10 promotes CTL responses in humans.
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Nizzoli
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.|Dipartimento di Fisiopatologia Medico Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Larghi
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Paroni
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Crosti
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Moro
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Petra
authors.initials: P
authors.lastname: Neddermann
authors.affiliation: Dipartimento di Fisiopatologia Medico Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.|Unità Operativa di Gastroenterologia ed Endoscopia, Fondazione IRCCS Cà Granda Ospedale Policlinico, Milan, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Caprioli
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.|Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pagani
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Francesco
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.|DISCCO, Dipartimento di Scienze cliniche e di comunità, Università degli Studi di Milano, Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.affiliation: Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D018949:Antigens, CD1 / Q000378:metabolism*; D019898:Autocrine Communication / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D045142:Cross-Priming / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; C437944:CD1C protein, human; D016207:Cytokines; D006023:Glycoproteins; D015234:HLA-A Antigens; D018836:Inflammation Mediators; D016753:Interleukin-10
keywords: Cross presentation/priming; Dendritic cells; Interleukin-10; Regulatory T cells; cytotoxic T cells