Vossenkaemper, Anna and Hundsrucker, Christian and Page, Kevin and van Maurik, Andre and Sanders, Theodore J. and Stagg, Andrew J. and Das, Lisa and MacDonald, Thomas T. (2014) A CD3-Specific Antibody Reduces Cytokine Production and Alters Phosphoprotein Profiles in Intestinal Tissues From Patients With Inflammatory Bowel Disease. GASTROENTEROLOGY, 147 (1). pp. 172-183. ISSN 0016-5085, 1528-0012
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND & AIMS: T cells mediate the development of inflammation in inflammatory bowel disease (IBD). We investigated the effects of an antibody against CD3 called otelixizumab, which induces immune tolerance, in intestinal mucosa samples from patients. METHODS: Intestinal tissues were isolated from patients undergoing routine endoscopy or from patients undergoing intestinal surgery for colon cancer or IBD; healthy surrounding tissues were collected as controls. Isolated lamina propria mononuclear cells (LPMCs) and mucosal tissue explants were incubated with otelixizumab for 24 or 48 hours. Production of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. Levels of 36 cytokines and chemokines and phosphorylation of 39 receptor tyrosine kinases and signaling molecules were measured using protein arrays. Immunoblot analysis was used to analyze T-cell transcription factors. RESULTS: Incubation of intestinal tissues or LPMCs with otelixizumab reduced production of interferon gamma, interleukin (IL)-17A, and other inflammatory cytokines and chemokines, simultaneously increasing production of IL-10. Mucosal biopsy specimens from patients with IBD retained inflammation-associated tyrosine phosphoprotein profiles ex vivo. Incubation of the inflamed tissue with otelixizumab reduced phosphorylation of these proteins to levels observed in control tissues. Otelixizumab also markedly reduced phosphorylation of proteins associated with T-cell receptor activation. Neutralization of IL-10 blocked the anti-inflammatory effects of otelixizumab. CONCLUSIONS: We observed anti-inflammatory effects of anti-CD3 in inflamed intestinal tissues from patients with IBD. The antibody appears to down-regulate T-cell activation via IL-10.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTI-CD3 MONOCLONAL-ANTIBODY; RECOMBINANT HUMAN INTERLEUKIN-10; VERSUS-HOST-DISEASE; T-CELLS; HUMANIZED ANTI-CD3; DOSE-ESCALATION; BONE-MARROW; PHASE-I; OKT3; VISILIZUMAB; Crohn's Disease; Ulcerative Colitis; Immune Regulation; IFN |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Oct 2019 11:38 |
| Last Modified: | 17 Oct 2019 11:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9970 |
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