Increased transplant arteriosclerosis in the absence of CCR7 is associated with reduced expression of Foxp3
Abstract
The chemokine receptor CCR7 plays a pivotal role in the homing of naïve T cells and regulatory T cells to secondary lymphoid organs and the migration of dendritic cells into afferent lymphatic vessels. Antigen presentation, T cell recruitment, and expansion of regulatory cells are crucial events in establishing and controlling chronic allograft dysfunction. In this study, we report an important role for chemokine receptor CCR7 in the development of transplant arteriosclerosis. Fully major histocompatibility complex-mismatched CBA (H2) donor aortas were transplanted into BALB/c-CCR7 (H2), BALB/c-CCR7 (H2), or BALB/c-CCR7 (H2) recipients. Grafts were analyzed by histology, morphometry, and immunofluorescence on day 30 after transplantation. Intragraft cytokine mRNA production was analyzed by realtime polymerase chain reaction on day 14 after transplantation. After implanting fully major histocompatibility complex-mismatched donor aortas into CCR7-deficient recipients, transplant arteriosclerosis was significantly elevated. CD4 depletion resulted in a reduction of intima proliferation in CCR7 recipients whereas CD8 depletion had no effect. Analysis of aortic grafts from CCR7 recipients revealed high numbers of infiltrating CD4, F4...Continue Reading
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