Differential effect of IL-10 on dendritic cell-induced T cell proliferation and IFN-gamma production.

Abstract

IL-10 has previously been shown to inhibit cytokine production by Th1 cells by blocking macrophage accessory cell function. In this study we demonstrate that dendritic cell-induced Th1 proliferation was unaffected by IL-10, whereas macrophage-stimulated proliferation was inhibited in the same system. In contrast dendritic cell induced IFN-gamma production by the Th1 clones was down-regulated by IL-10. Inasmuch as dendritic cells have been shown to be potent APC for T cells in primary responses we determined the effect of IL-10 on dendritic cell-induced proliferation and IFN-gamma production by CD4+ and CD8+ T cells. Dendritic cells were effective at stimulating both proliferation and IFN-gamma secretion of CD4+ or CD8+ T cells in a primary allogeneic mixed leukocyte response. In contrast, IL-10 markedly inhibited dendritic cell driven IFN-gamma production by purified CD4+ and CD8+ T cells. Down-regulation of dendritic cell-induced IFN-gamma production suggests a role for IL-10 in inhibiting the initiation of cell-mediated immune responses.

Circumventing pyroptosis via hyperactivation shapes superior immune responses of human type 2 dendritic cells compared to type 3 dendritic cells

“…Enhanced IL‐10 secretion by DC3 might also negatively influence the restimulation of T cell responses, as it has been shown to reduce proliferation and IL‐2 secretion by T cells [44–46]. However, IL‐10 also influences cytokine secretion by T cells and shifts the polarization into T H 2 as well as T reg cells [44, 47, 48]. As DC3‐induced T cells did not show enhanced production of IL‐4 or IL‐10 (Figs.…”

“…The differences observed in cytokine secretion and costimulatory molecule expression between DC2 and DC3 might be due to regulation at the posttranscriptional level, as Girard et al demonstrated that stimulation with IFNβ induces comparable activation of NFκB as well as a shared maturation program but leads to differential expression of the costimulatory molecules GITRL and CD86 on DC2 and DC3 [43]. Enhanced IL-10 secretion by DC3 might also negatively influence the restimulation of T cell responses, as it has been shown to reduce proliferation and IL-2 secretion by T cells [44][45][46]. However, IL-10 also influences cytokine secretion by T cells and shifts the polarization into T H 2 as well as T reg cells [44,47,48].…”

Sonic vibration ameliorates inflammatory diseases via the up-regulation of IL-10

“…IL-10 initiates a robust immunosuppressive response in innate immune cells, including macrophages, by regulating the transcription of cytokines and chemokines, and it inhibits the generation of reactive oxygen species during pathogenic infections (Bogdan et al 1991 ; Saraiva et al 2020 ). IL-10 indirectly inhibits T cell responses by suppressing antigen-presenting cells and directly regulates memory/effect T cells and T helper 17 cells (Macatonia et al 1993 ; Huber et al 2011 ; Kamanaka et al 2011 ). Consequently, research on disease therapy through the modulation of IL-10 is actively underway (Saraiva et al 2020 ).…”

Targeting inflammation as cancer therapy

“…IL-10 was initially conceived as a secreted cytokine synthesis inhibitory factor, known to inhibit cytokine production of Th1 cells [178] and activate macrophages and DCs [179,180]. As a key mediator of the anti-inflammatory response, IL-10 family cytokines are mostly produced by leukocytes, as well as human tumor cells.…”