Cytokines often display pleiotropic effects, and further studies will be necessary to appreciate fully the role of IL-17, which is not a single cytokine but represents a system of several subforms and receptors. In addition, the role of this cytokine family may change over the course of infection, and CD4+ T cells

may alternate between Treg and Th17 function [38]. The discrepant findings with IL-17 highlight that different types of inflammatory responses exist, and context has to be carefully assessed. Work by Sayi et al. [53] corroborated the correlation between long-term increased PD-0332991 mw inflammation and reduced bacterial colonization, in this case by Helicobacter felis. Given that H. felis promotes long-term inflammatory reactions and pre-cancerous changes that are not conducive to eliminating the pathogen, the authors stress the view that vaccine-mediated protection may rely on pro-inflammatory Th cells such as Th1 cells that seem also involved in promoting cancerous changes if bacteria cannot be eliminated. This idea is seemingly enforced by findings of Stoicov et al. [54] which show that mice deficient in T-bet, the transcription factor required for Th1 differentiation, do not develop cancerous lesions. Yet one cannot rule out the possibility that this is largely because of effects of T-bet

in cells other than Th1 cells. To date, however, histologic analyses of gastric inflammation in human volunteers immunized and challenged with H. pylori did not reproduce evidence for increased gastritis, at least during the first 2–3 months selleck products postinfection [33]. Th1, Th2, Th17, and Treg cells have all been detected in H. pylori infection. But our comprehension of the network

of pro-inflammatory Th1 click here and Th17 and regulatory Treg cells remains incomplete. We should be encouraged to improve our understanding of these networks as they seem to be critical for clinical outcomes. We will also be curious to see whether IL-9 or IL-22 producing Th cells and, in particular the newly discovered follicular helper CD4+ T cells (Tfh, [55]) also play a role in H. pylori infection, the latter in particular when infection leads to MALT lymphoma. Since the first proof-of-principle nearly 20 years ago [56,57], the development of a vaccine against H. pylori (for review, see [58]) remains a desirable option, because of cost-efficiency, to control H. pylori infection [59]. Although originally thought to be antibody-dependent, it was later shown that protection by active immunization required Th cells [36], and antibodies are not helpful or even counter-protective [60,61]. Clinical studies that combined vaccination with experimental infection with cagPAI-negative H. pylori indicated that T-cell immunity exists but that the vaccines tested required much improvement [33]. Improvement strategies would clearly benefit from a molecular understanding of the events that link Th cells with the effector mechanisms for protection.