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We aimed to study intestinal immune activation status in juvenile idiopathic arthritis ( JIA) by assessing intestinal human leucocyte antigen ( HLA) class II expression and the mRNA expression levels of the pro- and anti-inflammatory mediators and pattern recognition receptors. HLA- D-related ( HLA-DR) expression was assessed using immunohistochemical staining of frozen sections in 11 children with JIA and 17 controls. The gene expression levels of the anti- and proinflammatory cytokines, lymphocyte recognition receptors and pattern recognition receptors were studied with reverse transcription-polymerase chain reaction ( RT- PCR) in 14 children with JIA and 12 controls. All subjects had various gastrointestinal ( GI) symptoms indicating endoscopic examinations, but eventually were not diagnosed with GI disease. In JIA patients, the expression of HLA- DR was increased in the crypt epithelial cells and in the epithelial basement membrane of the ileum when compared with the controls. Positive HLA- DR staining in the ileal mucosa was associated with the presence of high clinical disease activity of JIA and low mRNA expression of anti-inflammatory mediators, such as forkhead box protein P3 ( FoxP3), glucocorticoid-induced tumour necrosis factor receptor-related protein ( GITR) and transforming growth factor ( TGF)-beta. Low ileal expression of interleukin ( IL)-10, TGF-β, FoxP3, Toll-like receptor 2 ( TLR-2) and TLR-4 transcripts correlated significantly with a high clinical disease activity in the JIA patients. The increased HLA- DR expression suggests enhanced intestinal antigen presentation in JIA. A correlation between clinical disease activity and low gene expression of tolerogenic mediators in the ileum supports the hypothesis that a link exists between the gut immune system and JIA. [ABSTRACT FROM AUTHOR]

In order to characterize T cell responses in human Helicobacter pylori infection, we have examined proliferative responses and cytokine production by CD4+ and CD8+ T cells isolated from duodenal ulcer patients and asymptomatic H. pylori carriers, after activation with some H. pylori antigens that may be important in disease development. For control purposes, T cells from uninfected volunteers were also examined. The different H. pylori antigens induced only modest proliferative responses in circulating CD4+ and CD8+ T cells from both H. pylori-infected and uninfected individuals. However, circulating T cells from H. pylori-infected subjects produced larger amounts of interferon-gamma (IFN-γ) in response to the Helicobacter antigens than did T cells from uninfected volunteers. Furthermore, CD8+ T cells produced larger amounts of IFN-γ than did CD4+ T cells, on a per cell basis. Most IFN-γ-producing cells from both infected and uninfected volunteers appeared to be naive T cells expressing CD45RA. Increased production of IL-4 and IL-5 was, on the other hand, only seen in a few instances after stimulation of isolated CD4+ and CD8+ T cells. Stimulation of freshly isolated gastric T cells with the different H. pylori antigens did not result in increased proliferation or cytokine production. In conclusion, our results show that several different purified H. pylori antigens induce production of IFN-γ, preferentially by CD8+ cells. Therefore, they suggest that IFN-γ-secreting CD8+ cells contribute significantly to the cytokine response induced by H. pylori infection. [ABSTRACT FROM AUTHOR]

A whole inactivated H. pylori bacterium preparation was found to stimulate blood mononuclear cells from both antibody-positive and antibody-negative subjects, but the antibody-positive subjects tended to have lower proliferation responses. The present study was designed to characterize T cell activation further by measuring several components of the response. Eighty-seven subjects (80 dyspeptic patients and seven healthy persons from the laboratory staff) with or without antibodies to H. pylori were studied by measuring the DNA synthesis induced by several H. pylori concentrations (1-23 μg/ml) and the control stimulants PPD, tetanus toxoid and pokeweed mitogen (PWM). H. pylori-induced secretion of interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), soluble CD8 and IL-2 receptor (IL-2R) molecules and H. pylori- and PPD-induced appearances of IL-2R+ and HLA-DR+ T cells were measured in a smaller number of subjects. H. pylori-induced DNA synthesis was again lower in the antibody/bacterium-positive subjects, while no differences between the two groups were found in cultures stimulated by unrelated antigens or PWM. Soluble IL-2R and TNF-α were detectable in cultures with H. pylori from all subjects, while the amount of IL-2 did not differ from that in the background culture. No differences were found in the amounts of IL-2 or soluble IL-2R between the antibody-positive and negative subjects; while the former tended to secrete more soluble CD8 molecules, a difference which was significant with the smaller H. pylori concentration used (P < 0.01). The numbers of HLA-DR+ and IL-2R+ T cells increased in cultures with H. pylori or PPD from all the subjects, the majority of both cells having the CD4 phenotype. Numbers of DR+ and IL-2R+ T cells were similar in the cultures of the antibody-positive and negative subjects, but the respective CD8 subsets were increased in the former. The confirmed decrease in proliferation in the antibody-positive subjects does not seem to be connected with lower IL-2/IL-2R responses but may involve CD8 cell activation. [ABSTRACT FROM AUTHOR]