| Anti-thymoglobulin (ATG) treatment does not reverse type 1 diabetes in the acute virally induced rat insulin promoter-lymphocytic choriomeningitis virus (RIP-LCMV) model. | |
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MedLine Citation:
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PMID: 21235534 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Immune modulators such as anti-thymoglobulin (ATG) are under clinical evaluation for the treatment of type 1 diabetes (T1D). Although such agents have cured T1D in the non-obese diabetic (NOD) model, their clinical efficacy has been much lower. In order to improve the odds of successful translation from bench to bedside, we propose to evaluate this agent under more stringent conditions. Here, we evaluated the capacity of ATG to reverse T1D in the acute rat insulin promoter-lymphocytic choriomeningitis virus (RIP-LCMV) model. RIP-LCMV-glycoprotein (GP) mice were treated after new-onset T1D with murine ATG antibodies. Although ATG treatment did not impair viral clearance it failed to reverse new-onset T1D in this model. The CD4:CD8 ratio was reduced drastically upon LCMV infection due to an expansion of CD8 effectors but ameliorated in ATG-treated mice. Although the percentage of CD4(+) CD25(+) regulatory T cells (T(regs) ) within the CD4(+) population was increased significantly after ATG therapy, their frequency in the periphery was reduced dramatically and never returned to normal baseline. The inability of ATG treatment to cure T1D in a stringent viral model (RIP-LCMV mice) is due at least partially to the inability to maintain or increase a sufficient CD4(+) CD25(+) T(regs) frequency, in striking contrast with what was reported in the NOD model. Our data would argue for the use of multiple animal models to assess efficacy of promising immune-based interventions and select the most potent therapies for future clinical trials. |
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Authors:
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D Bresson; M G von Herrath |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-01-14 |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 163 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-09 Completed Date: 2011-04-18 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 375-80 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology. |
Affiliation:
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Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antilymphocyte Serum / administration & dosage, therapeutic use* Blood Glucose / metabolism CD4-CD8 Ratio CD4-Positive T-Lymphocytes / immunology, pathology CD8-Positive T-Lymphocytes / immunology, pathology Diabetes Mellitus, Type 1 / blood, etiology, immunology, therapy* Disease Models, Animal Insulin / genetics* Interleukin-2 Receptor alpha Subunit / metabolism Kinetics Lymphocyte Count Lymphocyte Depletion Lymphocytic choriomeningitis virus / genetics*, isolation & purification Mice Mice, Inbred C57BL Mice, Transgenic Promoter Regions, Genetic / genetics* Rats T-Lymphocyte Subsets / immunology, metabolism, pathology T-Lymphocytes, Regulatory / immunology, metabolism, pathology Treatment Outcome Viral Load / immunology |
| Chemical | |
Reg. No./Substance:
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0/Antilymphocyte Serum; 0/Blood Glucose; 0/Il2ra protein, mouse; 0/Insulin; 0/Interleukin-2 Receptor alpha Subunit |
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