Achieving antigen-specific tolerance in diabetes: regulating specifically.
Autoreactive T cells that escape negative selection in the thymus do not normally cause productive immune responses to self-antigens because of a number of regulatory mechanisms. Studies with anti-CD3 monoclonal antibodies (mAbs) have suggested that immune regulatory mechanisms are induced by drug treatments that are able to stop on-going unwanted immune responses, such as type 1 diabetes, involving induction of regulatory T cells. TGF-beta dependent and independent mechanisms have been described involving CD4(+) as well as CD8(+) T cells. The challenge is now to apply these mechanisms in an antigen-specific manner and so that lasting tolerance to the autoimmune responses can be maintained. We discuss recent data concerning the mechanisms of anti-CD3 mAb treatment and the ways in which our understanding of these mechanisms can be used to develop adoptive immune therapy with regulatory T cells to treat patients with type 1 diabetes or other autoimmune diseases.
Chen
Wei
W
Naomi Berrie Diabetes Center and the Division of Endocrinology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. kh318@columbia.edu
Bluestone
Jeffrey A
JA
Herold
Kevan C
KC
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive; D008212:Lymphocyte Depletion; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell