5a) In addition, IL-1β was capable of mediating its affect in th

5a). In addition, IL-1β was capable of mediating its affect in the absence of DCs and could amplify anti-CD3/CD28-mediated Treg proliferation at concentrations as low as 100 pg/ml, lower than the amount of IL-1β produced naturally by H. pylori-treated DCs (Fig. 5b).

We confirmed the role of IL-1β in HpDC-induced see more Treg proliferation by stimulating Tregs with HpDCs in the presence of a neutralizing IL-1RA. The addition of IL-1RA inhibited Treg proliferation, while anti-IL-6 and anti-TNFRII antibodies had no effect (Fig. 5c). These results suggest that IL-1β is the key inflammatory cytokine produced by DCs in response to H. pylori that is responsible for Treg expansion. Suppression of pathogen-responsive Teffs by Tregs at a site of infection is key to determining pathogen persistence/clearance and the degree of tissue injury caused by local inflammation. To determine, therefore, whether H. pylori affects the suppressive capacity of Tregs, ImmDcs and HpDCs were used to stimulate allogeneic Teff in the presence and absence of 1:1 Tregs for 5 days and suppression of proliferation calculated. HpDCs impaired suppression by Tregs when compared to co-cultures selleck chemical stimulated with ImmDCs (Fig. 6a). To rule out the possibility that proliferation of Teff impurities in the

Treg population caused an apparent loss of suppression, we repeated the experiments with CD25hi Tregs and CD4+CD25− Teff FACS-sorted to >98% purity. As before, suppression of Teffs was still impaired significantly by HpDCs (Fig. 6b). To determine whether the loss of suppression was mediated

by IL-1β, Tregs and Teffs were co-cultured at a 1:1 ratio and activated with HpDCs in the presence of IL-1RA. Antagonism of IL-1β resulted find more in partial restoration of suppression (Fig. 6c), suggesting that suppression of Teffs by Tregs is abrogated by IL-1β produced by HpDC. To determine the capacity of Tregs to inhibit the effector function of Teffs, we measured proinflammatory cytokine concentrations in supernatants of Teffs, Tregs and 1:1 Treg : Teff co-cultures stimulated by immDCs or HpDCs. IL-17 production was not detectable in this system, and IFN-γ production was not inhibited by Tregs in co-cultures stimulated with HpDCs, whereas ImmDC-stimulated Tregs could suppress IFN-γ production. (Fig. 6d). Taken together, these data demonstrate that the presence of H. pylori instructs DCs to inhibit Treg-mediated suppression of Teffs in an IL-1β-mediated manner. Persistence of H. pylori is the result of both resistance against the local gastric microenvironment and immunological evasion [32]. Despite making physical contact with immune cells in the lamina propria [33], H. pylori evades immune clearance through a variety of mechanisms including its unique site of colonization, modulation of adhesion and alteration of the host immune response [34]. H.

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