Treatment of Type 1 diabetes with anti-CD3 monoclonal antibody: induction of immune regulation?
Anti-CD3 monoclonal antibodies (MAbs) were developed as a way of inducing immune suppression of T cells. More recent studies have indicated that anti-CD3 MAbs can affect immune responses by inducing immune regulation. We recently reported that a single course of treatment with a non-FcR binding anti-CD3 MAb, hOKT3gamma1(Ala-Ala), can lead to preservation of insulin production in patients with new-onset Type 1 diabetes for even beyond 1 yr after treatment. The sustained insulin production was accompanied by improvement in glucose control and reduced use of insulin. Our studies of the mechanism of the non-FcR binding anti-CD3 MAb indicate that the MAb delivers an activation signal to T cells resulting in disproportionate production of interleukin-10 (IL-10) relative to interferon-gamma(IFN-gamma) in vitro compared with FcR binding anti-CD3 MAb, and detectable levels of IL-10, IL-5, but rarely IFN-gamma or IL-2 in the serum after treatment. In addition, the drug induces a population of CD4+IL-10+ CCR4+ cells in vivo. Preclinical data suggest that anti-CD3 MAb induces a population of regulatory T cells that can prevent or lead to reversal of Type 1 diabetes. The induction of cells with a regulatory phenotype may account for the ability of anti-CD3 MAb to induce immune regulation.
Herold
Kevan C
KC
Department of Medicine, the Naomi Berrie Diabetes Center, and the Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. kh318@columbia.edu
Taylor
Lesley
L
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000096:biosynthesis; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D015704:CD4 Antigens / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D017252:CD3 Complex; D015704:CD4 Antigens; D007328:Insulin; D007378:Interleukins; D007371:Interferon-gamma