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...

Full description

Saved in:
Bibliographic Details
Published in:Immunologic research 2003-01, Vol.28 (2), p.141-150
Main Authors: Herold, Kevan C, Taylor, Lesley
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - therapeutic use
Blood Glucose - biosynthesis
CD3 Complex - immunology
CD3 Complex - metabolism
CD4 Antigens - biosynthesis
Diabetes
Diabetes Mellitus, Type 1 - immunology
Diabetes Mellitus, Type 1 - therapy
Humans
Immunology
Insulin - blood
Insulin - metabolism
Interferon-gamma - biosynthesis
Interleukins - biosynthesis
Medical research
Monoclonal antibodies
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0257-277X
0257-277X
1559-0755
DOI:10.1385/ir:28:2:141