Longitudinal Frequencies of Blood Leukocyte Subpopulations Differ between NOD and NOR Mice but Do Not Predict Diabetes in NOD Mice.

Tanja Telieps,Meike Köhler,Anette-Gabriele Ziegler,Kerstin Adler,Katharina Foertsch,Ezio Bonifacio,Martin Hrabě De Angelis,Thure Adler,Admar Verschoor,Dirk H Busch,Irina Treise

doi:10.1155/2016/4208156

Abstract

Immune phenotyping provides insight into disease pathogenesis and prognostic markers. Trajectories from age of 4 to 36 weeks were modeled for insulin autoantibodies and for leukocyte subpopulations in peripheral blood from female NOD (n = 58) and NOR (n = 22) mice. NOD mice had higher trajectories of insulin autoantibodies, CD4+ and CD8+ T lymphocytes, B lymphocytes, IgD+IgM− B lymphocytes, and NK cells and lower trajectories of CD4+CD25+ T lymphocytes, IgM+ B lymphocytes, granulocytes, and monocytes than NOR mice (all p < 0.001). Of these, only the increased IAA trajectory was observed in NOD mice that developed diabetes as compared to NOD mice that remained diabetes-free. Therefore, the profound differences in peripheral blood leukocyte proportions observed between the diabetes-prone NOD mice and the diabetes-resistant mice do not explain the variation in diabetes development within NOD mice and do not provide markers for diabetes prediction in this model.

Highlights

Type 1 diabetes is an autoimmune disease resulting from destruction of pancreatic ß-cells by infiltrating immune cells
The profound differences in peripheral blood leukocyte proportions observed between the diabetes-prone NOD mice and the diabetes-resistant mice do not explain the variation in diabetes development within NOD mice and do not provide markers for diabetes prediction in this model
It is possible that the extent of change may associate with the likelihood and rate of diabetes development in individual mice and that this may reveal markers that may help stratify Journal of Diabetes Research the rate of progression to diabetes in man

Summary

Introduction

Type 1 diabetes is an autoimmune disease resulting from destruction of pancreatic ß-cells by infiltrating immune cells. The NOD mouse is an important model of spontaneous autoimmune diabetes that has been used to understand type 1 diabetes pathogenesis and develop therapeutics to prevent ß-cell destruction [1]. NOD mice have alterations in leukocyte populations as compared to other mouse strains [4, 5]. We quantified leukocyte populations in peripheral blood from NOD and NOR mice in biweekly intervals from 4 weeks to 36 weeks of age or until diabetes onset. We compared trajectories of T cell and B cell subpopulations and of NK cells, granulocytes, and monocytes between NOD and NOR mice and within NOD mice that progressed and did not progress to diabetes

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Conclusion