Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, F4/80, and CD205 cells. Furthermore, intragraft cytokine production showed higher levels of interleukin-4, interleukin-12, and eotaxin mRNA expression, whereas significantly lower Foxp3 mRNA expression was observed in CCR7 recipients. CONCLUSION: These data suggest that although alloantigen presentation in secondary lymphoid organs is hampered in CCR7-deficient recipients, this process may take place within the allograft itself, leading to increased formation of transplant arteriosclerosis. The decrease in Foxp3 expression despite increased in CD4 T cell infiltration indicates a reduction in T regulatory cells possibly influencing the intensity of the graft rejection.

Original publication

DOI

10.1097/TP.0b013e3181826a97

Type

Journal article

Journal

Transplantation

Publication Date

27/08/2008

Volume

86

Pages

590 - 600

Keywords

Animals, Aorta, Arteriosclerosis, Forkhead Transcription Factors, Lymphocyte Count, Mice, Mice, Inbred CBA, Postoperative Complications, Receptors, CCR7, T-Lymphocytes, Regulatory, Transplantation, Homologous