deficiency of the metalloproteinase-disintegrin adam8 is associated with thymic hyper-cellularity缺乏的metalloproteinase-disintegrin adam8与胸腺hyper-cellularity相关联.pdfVIP

Deficiency of the Metalloproteinase-Disintegrin ADAM8 Is Associated with Thymic Hyper-Cellularity 1,3. 1,3. ¨ 3 1,2 Klaus Gossens , Silvia Naus , Georg A. Hollander , Hermann J. Ziltener * 1The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada, 2 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada, 3 Laboratory of Pediatric Immunology, Department of Biomedicine, University of Basel and The University Children’s Hospital (UKBB), Basel, Switzerland Abstract Background: Thymopoiesis requires thymocyte-stroma interactions and proteases that promote cell migration by degrading extracellular matrix and releasing essential cytokines and chemokines. A role for several members of the A Disintegrin and Metalloprotease (ADAM) family in T cell development has been reported in the past. Methodology/Principal Findings: Here, we present data indicating that the family member ADAM8 plays a role in thymic T cell development. We used qrtPCR on FACS sorted thymic subsets together with immunofluorescene to analyze thymic ADAM8 expression. We found that ADAM8 was expressed in murine thymic stromal cells and at lower levels in thymocytes where its expression increased as cell matured, suggesting involvement of ADAM8 in thymopoiesis. Further flow cytometry analysis revealed that ADAM8 deficient mice showed normal development and expansion of immature thymocyte subsets. There was however an intrathymic accumulation of single positive CD4 and CD8 T cells which was most noticeable in the late mature T cell subsets. Accumulation of single positive T cell