ABSTRACT
BACKGROUND & AIMS: An abnormal immune response may play a pathogenic role in Crohn's disease. The aim of this study was to determine the role of regulatory T cells in Crohn's disease. METHODS: T-cell phenotype and function were studied in blood lymphocytes from patients with Crohn's disease and a control group consisting of healthy donors and patients with ulcerative colitis. RESULTS: Flow cytometric studies showed a significant increase in the percentage of CD3+DR+ and CD4+CD45RO+ T cells in patients with Crohn's disease. T cells from patients with Crohn's disease and ulcerative colitis showed a defective proliferative response after stimulation with surface mitogenic ligands (phytohemagglutinin and anti-CD28 or anti-CD3 antibodies). Soluble interleukin-2 receptor alpha was augmented in the Crohn's disease and ulcerative colitis groups. In the Crohn's disease group, impairment of T-lymphocyte proliferation was normalized by exogenous interleukin 2, although endogenous interleukin-2 production and interleukin-2 receptor alpha expression were normal. CONCLUSIONS: An in vivo expansion of CD4+ T lymphocytes with memory phenotype and impaired T-cell proliferation that can be restored by pharmacological amounts of interleukin 2 was found in patients with Crohn's disease. There is a severe immunodisturbance in the T-cell compartment of patients with either clinically active or inactive Crohn's disease.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Crohn Disease/immunology , Leukocyte Common Antigens/analysis , Lymphocyte Activation , Adult , CD4-Positive T-Lymphocytes/metabolism , Colitis, Ulcerative/immunology , Crohn Disease/metabolism , Female , Flow Cytometry , Humans , Immunophenotyping , Interleukin-2/biosynthesis , Linear Models , Male , Middle Aged , Receptors, Interleukin-2/metabolism , SolubilityABSTRACT
There is increasing evidence that ulcerative colitis is associated with an abnormality of the immune system. Although the aetiology remains unknown, it has been suggested that the immune system of these patients is implicated in the pathogenesis of their disease. T cell function was investigated in ulcerative colitis patients and defective phytohaemagglutinin induced T cell mitogenesis was found. The DNA synthesis induced by stimulation with phorbol esters plus ionophore (ionomycin), however, was normal. These changes cannot be ascribed to either decreased interleukin 2 synthesis or to a defective interleukin 2 receptor expression after cellular activation. Moreover, this defective proliferative response of the T lymphocytes was observed even in the presence of saturated concentrations of exogenous interleukin 2. These results emphasise that the interleukin 2 dependent proliferation pathway is deficient in T lymphocytes from ulcerative colitis patients.
Subject(s)
Colitis, Ulcerative/immunology , Interleukin-2/metabolism , T-Lymphocytes/physiology , Adolescent , Adult , Aged , Cell Division/drug effects , Cell Division/immunology , Cell Membrane/immunology , Cells, Cultured , DNA/biosynthesis , Female , Humans , Ionomycin/pharmacology , Male , Middle Aged , Phytohemagglutinins/pharmacology , Receptors, Interleukin-2/metabolism , Stimulation, Chemical , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
On the basis of experimental investigations and clinical observations the authors recommend technical modes allowing to cover a low bleeding duodenal ulcer by the walls of the stomach and duodenum. Variants of draining operations (gastroduodeno-jejunoanastomosis, gastroduodenostomy) with simultaneous vagotomy are described in detail.
