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.
IL-10 promotes homeostatic proliferation of human CD8+ memory T cells and, when produced by CD1c+ DCs, shapes naive CD8+ T-cell priming / G. Nizzoli, P. Larghi, M. Paroni, M.C. Crosti, M. Moro, P. Neddermann, F. Caprioli, M. Pagani, R. De Francesco, S. Abrignani, J. Geginat. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - 46:7(2016 Jul), pp. 1622-1632.
|Titolo:||IL-10 promotes homeostatic proliferation of human CD8+ memory T cells and, when produced by CD1c+ DCs, shapes naive CD8+ T-cell priming|
NIZZOLI, GIULIA (Primo)
LARGHI, PAOLA (Secondo)
ABRIGNANI, SERGIO (Penultimo)
|Parole Chiave:||cross presentation/priming; cytotoxic T cells; dendritic cells; interleukin-10; regulatory T cells; immunology; immunology and allergy|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Data di pubblicazione:||lug-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/eji.201546136|
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