Helicobacter pylori-Mediated Protection from Allergy Is Associated with
IL-10-Secreting Peripheral Blood Regulatory T Cells
#MMPMID27014260
Hussain K
; Letley DP
; Greenaway AB
; Kenefeck R
; Winter JA
; Tomlinson W
; Rhead J
; Staples E
; Kaneko K
; Atherton JC
; Robinson K
Front Immunol
2016[]; 7
(?): 71
PMID27014260
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Helicobacter pylori infections are usually established in early childhood and
continuously stimulate immunity, including T-helper 1 (Th1), Th17, and regulatory
T-cell (Treg) responses, throughout life. Although known to be the major cause of
peptic ulcer disease and gastric cancer, disease occurs in a minority of those
who are infected. Recently, there has been much interest in beneficial effects
arising from infection with this pathogen. Published data robustly show that the
infection is protective against asthma in mouse models. Epidemiological studies
show that H. pylori is inversely associated with human allergy and asthma, but
there is a paucity of mechanistic data to explain this. Since Th1 and Treg
responses are reported to protect against allergic responses, we investigated if
there were links between the human systemic Th1 and Treg response to H. pylori
and allergen-specific IgE levels. The human cytokine and T-cell responses were
examined using peripheral blood mononuclear cells (PBMCs) from 49 infected and 58
uninfected adult patients. Concentrations of total and allergen-specific plasma
IgE were determined by ELISA and ImmunoCAP assays. These responses were analyzed
according to major virulence factor genotypes of the patients' colonizing H.
pylori strains. An in vitro assay was employed, using PBMCs from infected and
uninfected donors, to determine the role of Treg cytokines in the suppression of
IgE. Significantly higher frequencies of IL-10-secreting CD4(+)CD25(hi) Tregs,
but not H. pylori-specific Th1 cells, were present in the peripheral blood of
infected patients. Total and allergen-specific IgE concentrations were lower when
there was a strong Treg response, and blocking IL-10 in vitro dramatically
restored IgE responses. IgE concentrations were also significantly lower when
patients were infected with CagA(+) strains or those expressing the more active
i1 form of VacA. The systemic IL-10(+) Treg response is therefore likely to play
a role in H. pylori-mediated protection against allergy in humans.
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