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Immunoregulatory Effect of Anti-thymocyte Globulin Monotherapy on Peripheral Lymphoid Tissues of Non-obese Diabetic Mice.
MedLine Citation:
PMID:  22099776     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVE: Experimental and clinical studies have shown that autoimmunity-causing diabetes may be abrogated by immune intervention. Several anti-T-lymphocyte antibodies focus on distinct T-cell targets. We tested the effect of murine anti-thymocyte globulin (ATG; Genzyme, Framingham, MA) in peripheral lymphoid organs of non-obese diabetic (NOD) mice after the onset of hyperglycemia.
METHODS: Diabetic NOD mice were treated with two doses of ATG (1 mg totally) or maintained without treatment as controls. Blood glucose levels were monitored twice a week. The mice were terminated at day 0, 7, 14, or 28 after the initiation of the study. Subpopulations of T-lymphocytes and FoxP3+ (forkhead box P3 positive) regulatory T-cells were analyzed among elements isolated from the spleen and pancreatic lymph nodes.
RESULTS: Mice with blood glucose levels greater than 13 mmol/L were included in the study. Diabetes remission occurred in 16% (3/19) of mice treated with ATG. Only one case of remission was observed in the control group (6%; 1/16). ATG therapy a significantly decreased the CD8+/CD4+ T-lymphocyte ratio. Among splenocytes, a significant difference was detected only on day 7 (0.069 versus 0.198 T-lymphocyte ratio); in lymph nodes, a decrease was observed on day 28 (0.21 versus 0.51 T-lymphocytes ratio). The regulatory T-cells population increased after ATG administration compared with the control group at day 7 (16.2% versus 10.8% in CD4+ splenocytes; 20.7% versus 10.3% in CD4+ lymph node cells). However, the increased FoxP3+ cell population was not durable.
CONCLUSIONS: ATG treatment of diabetic NOD mice showed an immunoregulatory effect in peripheral lymphoid tissue with a significantly deceased CD8+/CD4+ ratio, which, however, did not normalize the metabolic parameters in a short period after the onset of overt diabetes.
Authors:
L Vargova; K Zacharovova; E Dovolilova; L Vojtova; F Saudek
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation proceedings     Volume:  43     ISSN:  1873-2623     ISO Abbreviation:  Transplant. Proc.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0243532     Medline TA:  Transplant Proc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3277-80     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Diabetes Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
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