期刊
CLINICAL IMMUNOLOGY
卷 156, 期 1, 页码 1-8出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2014.10.004
关键词
Sjogren's Syndrome; Chimera; Animal model; Humanized mouse
类别
资金
- The Ohio State University's Wexner Medical Center
- Richmond Eye and Ear Foundation
- CTSA [UL1TR000090]
- National Cancer Institute [P30 CA016058]
Despite recent advances in the understanding of Sjogren's Syndrome (SjS), the pathogenic mechanisms remain elusive and an ideal model for early drug discovery is not yet available. To establish a humanized mouse model of SjS, peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with SjS were transferred into immunodeficient NOD-scid IL-2r gamma(null) mouse recipients to produce chimeric mice. While no difference was observed in the distribution of cells, chimeric mice transferred with PBMCs from SjS patients produced enhanced cytokine levels, most significantly IFN-gamma and IL-10. Histological examination revealed enhanced inflammatory responses in the lacrimal and salivary glands of SjS chimeras, as measured by digital image analysis and blinded histopathological scoring. Infiltrates were primarily CD4+, with minimal detection of CD8+ T-cells and B-cells. These results demonstrate a novel chimeric mouse model of human SjS that provides a unique in vivo environment to test experimental therapeutics and investigate T-cell disease pathology. (C) 2014 The Authors. Published by Elsevier Inc.
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