Clinical application of human CD4+ CD25+ regulatory T cells for the treatment of inflammatory bowel diseases.
As our understanding of the immunological and genetic basis of inflammatory bowel disease (IBD) grows, potential therapeutic options are being developed at a rapid pace. Nevertheless, new drugs for IBD are needed because about half of all patients with severe ulcerative colitis (UC) eventually undergo colectomy, and a significant part of Crohn's disease (CD) patients do not respond to standard medical therapies, including immunosuppressants and TNF-alpha neutralising antibodies, or suffer from significant side effects. Finally, recurrence of disease activity following remission is frequent in both UC and CD, and there is an unmet need for effective maintenance strategies. It is well-known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only does active suppression by regulatory T (TR) cells play an important role in the normal intestinal homeostasis, but also its dysregulation might lead to the development of IBD. TR cells are functional subsets of T cells that downregulate adaptive immune responses by interfering with the activation of dendritic cells and proliferation of T cells. From experimental work it is now clear that TR cells play a critical role in maintaining immune homeostasis, and several therapeutic approaches have been targeted at the induction of TR cells in order to control mucosal inflammation. Before using TR cells clinically as living immunosuppressants for the treatment of IBD, however, we have to pass many critical checkpoints, such as the in vitro expansion of TR cells and the confirmation of their safety. This paper will discuss recently gained knowledge of human TR cells and the possibility of their clinical usages as a new strategy for the treatment of IBD.
Kanai
Takanori
T
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Graduate School of Medicine, 1-5-45 Yushima, Tokyo 113-8519, Japan. taka.gast@tmd.ac.jp
Watanabe
Mamoru
M
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000628:therapy; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015375:Receptors, Interleukin-2