The expression of OX40 in immunologically mediated diseases of the gastrointestinal tract (celiac disease, Crohn's disease, ulcerative colitis)

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Abstract
The membrane bound receptor OX40 (CD134) — a member of the TNF-R/NGF-R superfamily — is expressed on activated CD4+-T cells in humans and rodents. The interaction of OX40 with its ligand (OX40L) has been shown to be important in T-cell dependent B cell-stimulation and T-cell costimulation in vitro and in vivo. Several studies in experimental animal models for immunologically mediated GI-diseases have stressed the important role of the OX40–OX40L interaction for their manifestations. To assess if the OX40–OX40L interaction is also crucial in the pathogenesis of immunologically mediated diseases of the human gastrointestinal tract (e.g. celiac disease, Crohn's disease, ulcerative colitis) we investigated, in a first line of experiments, the expression of OX40 in biopsy specimens of patients suffering from these diseases. The biopsies were formalin fixed and paraffin-embedded and cut into 5 μm slides. To demask the antigen, the slides were consecutively cooked in citrate buffer for 20 min. Binding of anti-OX40 antibody was detected using the alkaline phosphatase-anti-alkaline phosphatease (APAAP) method. Nine of 11 biopsy specimens of patients with celiac disease were OX40-positive; none of the 20 control duodenal biopsies demonstrated OX40-positivity; and all biopsies of patients with ulcerative colitis (n = 11) or Crohn's disease (n = 11), respectively, stained positively for OX40. One of the 20 control biopsies showed OX40 staining. OX40 is highly expressed in the gastrointestinal tissue of patients with immunologically mediated bowel diseases. Together with previous studies in animal models for these diseases, the present results point to a potential role of OX40 in their pathogenesis.