Document Detail


Antibody combination therapy targeting CD25, CD70 and CD8 reduces islet inflammation and improves glycaemia in diabetic mice.
MedLine Citation:
PMID:  23039884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Destruction of pancreatic islets in type 1 diabetes is caused by infiltrating, primed and activated T cells. In a clinical setting this autoimmune process is already in an advanced stage before intervention therapy can be administered. Therefore, an effective intervention needs to reduce islet inflammation and preserve any remaining islet function. In this study we have investigated the role of targeting activated T cells in reversing autoimmune diabetes. A combination therapy consisting of CD25-, CD70- and CD8-specific monoclonal antibodies was administered to non-obese diabetic (NOD) mice with either new-onset diabetes or with advanced diabetes. In NOD mice with new-onset diabetes antibody combination treatment reversed hyperglycaemia and achieved long-term protection from diabetes (blood glucose <13·9 mmol/l) in >50% of mice. In contrast, in the control, untreated group blood glucose levels continued to increase and none of the mice were protected from diabetes (P < 0·0001). Starting therapy early when hyperglycaemia was relatively mild proved critical, as the mice with advanced diabetes showed less efficient control of blood glucose and shorter life span. Histological analysis (insulitis score) showed islet preservation and reduced immune infiltration in all treated groups, compared to their controls. In conclusion, antibody combination therapy that targets CD25, CD70 and CD8 results in decreased islet infiltration and improved blood glucose levels in NOD mice with established diabetes.
Authors:
T Alkhamis; J Barbic; T Crnogorac-Jurcevic; R E Greenlaw; M Peakman; S Jurcevic
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  170     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2013-03-18     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  139-48     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology.
Affiliation:
Medical Research Council (MRC) Centre for Transplantation, King's Health Partners Department of Immunobiology, King's College London, Guy's Hospital Barts Cancer Institute, Queen Mary, University of London, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology,  pharmacology*
Antibody Specificity
Antigens, CD / immunology*
Antigens, CD70 / immunology
Antigens, CD8 / immunology
Blood Glucose / immunology
Diabetes Mellitus, Experimental / blood,  immunology,  therapy*
Diabetes Mellitus, Type 1 / blood,  immunology,  therapy*
Female
Hyperglycemia / blood,  immunology,  therapy*
Inflammation / blood,  immunology,  therapy*
Interleukin-2 Receptor alpha Subunit / immunology
Islets of Langerhans / immunology
Lymphocyte Activation / immunology
Mice
Mice, Inbred NOD
T-Lymphocytes / immunology
Grant Support
ID/Acronym/Agency:
//Medical Research Council
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD; 0/Antigens, CD70; 0/Antigens, CD8; 0/Blood Glucose; 0/Interleukin-2 Receptor alpha Subunit
Comments/Corrections

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