Methods for Inducing Immune Tolerance Using Anti-CD3 therapeutics

BACKGROUND: Many treatments for autoimmune disease and transplantation rejection cause non-specific inhibition of the immune system (immunosuppression), which can lead to side effects and also has the limitation that once treatment is discontinued, symptoms of the disease may immediately return. The CD3 complex associates with the T cell receptor on the surface of T cells and is involved in antigen recognition. Anti-CD3 antibodies are currently of interest as an alternative to immunosuppressive methods because anti-CD3 treatments can induce long-term antigen-specific immunologic tolerance, which persists after treatment has stopped. Although anti-CD3 treatment shows promise, limitations in the duration and potency of its effects have led researchers to investigate methods for improving such immune tolerance.
DESCRIPTION: Co-administration of disease-specific antigens and anti-CD3 antibody in animal models of diabetes led to expansion of specific regulatory T cell populations and a reversal of disease onset, which was more potent than for anti-CD3 antibody alone. Identification and transplantation of the regulatory T cell population induced with auto-antigen and anti-CD3 antibody resulted in suppression of auto-aggressive T cells in the new host.
Researchers have also studied multiple subsets of regulatory T cells induced by anti-CD3 antibody alone, in vitro and in vivo. In vitro treatment of T cells with anti-CD3 antibody expands a particular subset of regulatory T cells, which has been characterized and may be involved in the long-term immune tolerance induced by anti-CD3 antibodies.