A regulatory instead of an IL-17 T response predominates in Helicobacter pylori-associated gastritis in children

Abstract

Th17 cells seem to have an important role in the efficacy of vaccines against Helicobacter pylori. Because children are a target group for human vaccination and Th17/T(reg) cells have intrinsically linked and antagonic commitments, we compared the gastric levels of Th17- and T(reg)-associated cytokines of children and adults. IL-6, IL-10 and TGF-β1 levels and Foxp3(+) cell numbers were higher, but IL-1β, IL-17A and IL-23 were lower in infected children than in infected adults. In conclusion T(reg) instead of Th17 cell response to H. pylori-infection predominates in children.

Complex T Cell Interactions Contribute to Helicobacter pylori Gastritis in Mice

“…Adoptive transfer of sufficiently large numbers of Treg overcomes this failure of engraftment and results in amelioration of gastritis in recipient mice. In combination with published data indicating that immunocompetent mice (22,46,47) and humans (17,19,20,48) mount a strong gastric T regulatory response to H. pylori colonization, to 8 months after infection. mRNA was isolated from gastric mucosa and cytokine expression quantified as described above.…”

“…It has become clear that hosts that mount a strong proinflammatory response are more likely to develop severe complications of disease, such as peptic ulcers or neoplasia (17), although the factors that determine which hosts will develop such responses remain unclear. In fact, the most recent evidence suggests that in humans, the primary response to infection is actually immunoregulatory (18)(19)(20)(21)(22). This finding supports many years of animal research indicating that suppression of regulatory responses is necessary for induction of severe disease (11,(23)(24)(25)(26)(27)(28)(29)(30)(31).…”

“…ϩ lymphocytes (Treg) are the principle modulators of gastritis due to H. pylori (17,(19)(20)(21)(22). In fact, some have suggested that the principle response of normal hosts to infection is regulatory rather than proinflammatory and is mediated by Treg (17,21,22).…”

Role of childhood infection in the sequelae ofH. pyloridisease

“…The reciprocal relationship between Treg responses and Th1 and Th17 responses in the gastric mucosa of H. pylori-infected children 79,96 is consistent with the ability of gastric Tregs to suppress H. pylori-induced T cell proliferation, IFN-γ and IL-17 production, and H. pylori-specific memory CD4 + T cells. [121][122][123] The consequence of a strong gastric Treg response in childhood H. pylori infection is a dampened effector cell response to the bacteria and diminished inflammatory damage, resulting in tolerance to the bacteria and persistence of the infection into adulthood.…”

“…131-133 Thus, the absence or near absence of H. pylori-induced inflammation in neonatal mice is the consequence of Treg-mediated suppression of the Th17 (and Th1) response, which corresponds to the Treg-mediated reductions in inflammation and IL-17 levels in children, 13,14,122 yet vaccine clearance of H. pylori is strongly IL-17-dependent. The confounding issue of reduced Th17 responses in young H. pylori-infected hosts but IL-17-dependence of effective vaccine eradication of the bacteria needs to be further clarified, since the global reduction in the prevalence of H. pylori will require immunization of children in order to prevent the complications of persistent infection.…”