期刊
FRONTIERS IN IMMUNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.01732
关键词
type 1 diabetes; NOD mouse; transgenic mouse model; B-lymphocyte phernotype; T-lymphocyte phernotype
类别
资金
- PlanNacional de I+D+i of the Spanish Ministry of Science and Innovation [SAF2016-77227-R]
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) that is an initiative from Instituto de Salud Carlos III (Spain)
- Juvenile Diabetes Research Foundation [5-2005-1133]
- University of Lleida
- IRBLleida
- FPI pre-doctoral fellowship from the Spanish Ministry of Science and Innovation [BES-2007-15221]
- NIH [DK46266, DK95735]
- Juvenile Diabetes Research Foundation
- American Diabetes Association
- Helmsley Charitable Trust [2014PG-T1D048]
Previous studies indicate that B-lymphocytes play a key role activating diabetogenic T-lymphocytes during the development of autoimmune diabetes. Recently, two transgenic NOD mouse models were generated: the NOD-PerIg and the 116C-NOD mice. In NOD-PerIg mice, B-lymphocytes acquire an activated proliferative phenotype and support accelerated autoimmune diabetes development. In contrast, in 116C-NOD mice, B-lymphocytes display an anergic-like phenotype delaying autoimmune diabetes onset and decreasing disease incidence. The present study further evaluates the T-and B-lymphocyte phenotype in both models. In islet-infiltrating B-lymphocytes (IIBLs) from 116C-NOD mice, the expression of H2-K-d and H2-Ag7 is decreased, whereas that of BAFF, BAFF-R, and TACI is increased. In contrast, IIBLs from NOD-PerIg show an increase in CD86 and FAS expression. In addition, islet-infiltrating T-lymphocytes (IITLs) from NOD-PerIg mice exhibit an increase in PD-1 expression. Moreover, proliferation assays indicate a high capacity of B-lymphocytes from NOD-PerIg mice to secrete high amounts of cytokines and induce T-lymphocyte activation compared to 116C B-lymphocytes. This functional variability between 116C and PerIg B-lymphocytes ultimately results in differences in the ability to shape T-lymphocyte phenotype. These results support the role of B-lymphocytes as key regulators of T-lymphocytes in autoimmune diabetes and provide essential information on the phenotypic characteristics of the T-and B-lymphocytes involved in the autoimmune response in autoimmune diabetes.
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