CCR7 expression by recipient T-cells and dendritic cells attenuates the development of transplant arteriosclerosis

Introduction: The chemokine receptor CCR7 plays a pivotal role in the recruitment of native T cells and antigen-activated dendritic cells (DCs) to secondary lymphoid organs. As antigen presentation and T cell recruitment are crucial events in allograft rejection, the aim of this study was to investigate the impact of CCR7 on the development of transplant arteriosclerosis.

Methods: Fully MHC mismatched CBA (H2k) donor aortas were transplanted into BALB/c- CCR7–/– (H2d), BALB/c-CCR7±(H2d) or BALB/c-CCR7+/+ (H2d) recipients. Grafts were analysed by histology, morphometry and immunofluorescence on day 30 after transplantation. Intra-graft cytokine and chemokine mRNA production was analysed by RT-PCR on day 14 after transplantation.

Results: Transplant arteriosclerosis was evident in both CCR7+/+ and CCR7±mice [intimal proliferation 59±8% (CCR7+/+) vs. 48±12% (CCR7±)] and significantly elevated in CCR7–/– recipients [intimal proliferation 82±9% (CCR7–/–) vs. 48±12% (CCR7±)] emphasising an important role for this receptor in this disease. CD4 depletion resulted in a significant reduction of intima proliferation in CCR7–/– recipients whilst CD8 depletion showed no effect. Analysis of the cellular infiltrate of CCR7–/– aortic grafts revealed significantly increased amounts of CD4+, F4/80+ and CD205+ cells as compared to CCR7±mice. Intra-graft cytokine production showed significantly higher IL-4, IL12 and eotaxin production and significantly lower iNOS and Foxp3 mRNA in CCR7–/– recipients.

Conclusion: These data suggest that expression of CCR7 by recipient T-cells and DCs play a protective role during the development of transplant arteriosclerosis. Absence of this receptor resulted in increased amounts of transplant arteriosclerosis, possibly mediated by infiltrating CD4+ T cells, IL4 and eotaxin.