Tolerance to islet autoantigens in type 1 diabetes

Tolerance to beta cell autoantigens represents a fragile equilibrium. Autor eactive T cells specific to these autoantigens are present in most normal i ndividuals but are kept under control by a number of peripheral tolerance m echanisms, among which CD4(+) CD25(+) CD62L(+) T cell-mediated regulation p robably plays a central role. The equilibrium may be disrupted by inappropr iate activation of autoantigen-specific T cells, notably following to local inflammation that enhances the expression of the various molecules contrib uting to antigen recognition by T cells. Even when T cell activation finall y overrides regulation, stimulation of regulatory cells by CD3 antibodies m ay reset the control of autoimmunity. Other procedures may also lead to dis ease prevention. These procedures are essentially focused on Th2 cytokines, whether used systemically or produced by Th2 cells after specific stimulat ion by autoantigens. Protection can also be obtained by NK T cell stimulati on. Administration of beta cell antigens or CD3 antibodies is now being tes ted in clinical trials in prediabetics and/or recently diagnosed diabetes.