Selective resistance of mucosal T-cell activation to immunosuppression in Crohn's disease

• Published in: Digestive and liver disease 2000-08, Vol.32 (6), p.484-494
• Main Authors: Matsuura, T., West, G.A., Levine, A.D., Fiocchi, C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Cell Death; Crohn Disease - immunology; Female; Humans; Immunosuppression; inflammatory bowel disease; Interleukin-2 - pharmacology; interleukin-4; Interleukin-4 - immunology; Interleukin-4 - pharmacology; Intestinal Mucosa - immunology; Lymphocyte Activation - immunology; Male; Middle Aged; Receptors, Interleukin-2 - physiology; T-cells; T-Lymphocytes - immunology
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/S1590-8658(00)80005-5

Background & Aims. The inappropriately high state of T-cell activation found in Crohn's disease could be due to failure to respond to inhibitory signals. We tested the hypothesis that Crohn's disease mucosal T-cells are resistant to the immunosuppressive action of interleukin-4. Patients. Patients with Crohn's disease, ulcerative colitis, and other malignant and non-malignant conditions undergoing bowel resection. Methods. The effect of interleukin-4 on lamina propria mononuclear cells from Crohn's disease, ulcerative colitis and control mucosa was assessed on various T-cell functions: interleukin-2-induced cytotoxicity, soluble interleukin-2 receptor and interleukin-2 production, and expression of mRNA for interleukin-2R and interferon-gamma. Results. Cytotoxicity of control and ulcerative colitis cells was markedly decreased by interleukin-4, whereas Crohn's disease cells failed to be inhibited. Addition of interleukin-4 to interleukin-2-stimulated cultures decreased soluble interleukin-2R production significantly less in Crohn's disease and ulcerative colitis than control cells. n the same cultures, residual levels of interleukin-2 were significantly increased in control and ulcerative colitis, but not Crohn's disease cultures. Finally, Crohn's disease cells were significantly more resistant to interleukin-4-mediated inhibition of spontaneous and interleukin-2-induced expression of interleukin-2Rα and interferon-gamma mRNA compared to control cells. Conclusions. The effector function, receptor expression and cytokine production of Crohn's disease mucosal T-cells are resistant to interleukin-4-mediated inhibition. Failure to respond to down-regulatory signals may contribute to persistent T-cell activation and chronicity of inflammation in Crohn's disease.