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. [10.1002/eji.201546136]

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
Primo
;
P. Larghi
Secondo
;
M. Paroni;F. Caprioli;M. Pagani;R. De Francesco;S. Abrignani
Penultimo
;
J. Geginat
2016

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.
cross presentation/priming; cytotoxic T cells; dendritic cells; interleukin-10; regulatory T cells; immunology; immunology and allergy
Settore MED/12 - Gastroenterologia
Article (author)
File in questo prodotto:
File Dimensione Formato  
Eur J Immunol 2016.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.3 MB
Formato Adobe PDF
1.3 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/420841
Citazioni
  • ???jsp.display-item.citation.pmc??? 19
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 35
social impact