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Altered immunoregulatory profile during anti-tumour necrosis factor treatment of patients with inflammatory bowel disease
Karolinska Institutet, Sweden.
Karolinska Institutet, Sweden.
Karolinska Institutet, Sweden.ORCID iD: 0000-0003-4822-3759
Karolinska Institutet, Sweden.
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2012 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 169, no 2, 137-147 p.Article in journal (Refereed) Published
Abstract [en]

Inflammatory bowel disease (IBD) can be treated effectively by anti-tumour necrosis factor (TNF) therapy. We set out to investigate the unclear immunoregulatory mechanisms of the treatment. Thirty-four patients with IBD treated with anti-TNF were included. Lymphocytes from peripheral blood and intestinal biopsies were analysed by flow cytometry. Regulation of antigen-stimulated proliferation was analysed by blocking of interleukin (IL)-10, transforming growth factor (TGF)-beta or depletion of CD25+ cells in peripheral blood mononuclear cell cultures. No changes in CD4+CD25+, CD25+TNF-RII+ or CD4+CD25+forkhead box protein 3 (FoxP3+) T cells could be observed in peripheral blood after, in comparison to before, 6 weeks of treatment. The suppressive ability of CD4+CD25+ cells did not change. There was an initial decrease of CD4+CD25+ cells in intestinal mucosa after 2 weeks of treatment, followed by an increase of these cells from weeks 2 to 6 of treatment (P < 0.05). This was accompanied by an increased percentage of CD69+ cells among these cells after 6 weeks of treatment compared to before treatment (P < 0.01). There was also an increase of mucosal T helper type1 cells from weeks 2 to 6 (P < 0.05). In addition, CD25+TNF-RII+ cells in the mucosa were decreased after 6 weeks of treatment compared to before treatment (P < 0.05). Before treatment, peripheral blood mononuclear cell baseline proliferation was increased when IL-10 was blocked (P < 0.01), but not after. In CD25+ cell-depleted cultures proliferation increased after treatment (P < 0.05). Our data indicate that anti-TNF treatment leads to an induction of effector T cells. Anti-TNF therapy has no significant impact on regulatory T cells in IBD, although the composition of regulatory T cell subsets may change during treatment.

Place, publisher, year, edition, pages
2012. Vol. 169, no 2, 137-147 p.
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:kth:diva-205249DOI: 10.1111/j.1365-2249.2012.04600.xISI: 000306124100008ScopusID: 2-s2.0-84863581114OAI: oai:DiVA.org:kth-205249DiVA: diva2:1088061
Note

QC 20170420

Available from: 2017-04-11 Created: 2017-04-11 Last updated: 2017-04-20Bibliographically approved

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