title: Targeting T and B lymphocytes in inflammatory bowel diseases: lessons from clinical trials.
abstract: Both innate and adaptive immunity play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). There is strong evidence that especially activated T cells initiate and perpetuate inflammation and tissue destruction. The increased numbers of CD4+ T cells in the intestinal wall of IBD patients may be explained by enhanced influx/activation and decreased apoptosis of these cells. Several studies have demonstrated that the gut-homing receptors CCR9 and α4β7 are selectively induced on T cells during their priming in intestinal inflamed sites. Whereas targeting of activated CD4+ T cells by specific antibody strategies or neutralization of key T-cell cytokines such as IL-2 or IFN-γ has not been effective in human IBD, blocking migration of activated leukocytes, e.g. T cells into the inflamed tissue by specific antibodies such as vedolizumab, seems highly effective. Recently it could also been demonstrated that administration of antigen-specific regulatory T cells to patients with refractory Crohn's disease was not only well tolerated but showed promising results. The role of B cells in human IBD is less clear. B-cell depletion has so far only been studied in ulcerative colitis where rituximab (anti-CD20) therapy failed. Therefore, although the therapeutic targeting of 'inflammatory' T and B cells was not successful in IBD, especially T cells remain key players in IBD. Targeting either T-cell migration or the use of regulatory T cells appears as the most promising 'T-cell-directed' therapies in the future.
authors.affiliation: Department of Internal Medicine I, Gastroenterology, Endocrinology and Metabolism, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: R R
authors.initials: RR
authors.lastname: Gerner
authors.forename: A R
authors.initials: AR
authors.lastname: Moschen
authors.forename: H
authors.initials: H
authors.lastname: Tilg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D002986:Clinical Trials as Topic; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal