PROLONGATION OF ALLOGRAFT SURVIVAL IN CCR7-DEFICIENT MICE

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Abstract

Background.

Lymphocyte homing to secondary lymphoid organs is thought to be required for initiation of the alloreactive immune response. Because CCR7 is the essential chemokine receptor responsible for lymphocyte and dendritic cell homing to secondary lymphoid organs, allograft survival was analyzed in CCR7-deficient (CCR7−/−) mice.

Methods.

Heterotopic heart and skin allotransplantation was performed in CCR7−/− and wild-type (WT) recipients. Graft survival was monitored daily. Grafts and draining lymph nodes were analyzed by immunohistology and flow cytometry at different time points. Groups of mice were splenectomized at the day of allotransplantation.

Results.

A significant though modest prolongation of allograft survival in CCR7−/− recipients was observed for heart grafts (WT, 7.3±0.5 days; CCR7−/−, 10.7±2.8 days) and skin grafts (WT, 8.9±0.9 days; CCR7−/−, 12.3±0.9 days). This was accompanied by a delay in the cellular infiltration of allografts. T-cell accumulation and expansion in the draining lymph nodes in CCR7−/− recipients was severely impaired. Splenectomy had only a moderate prolongation effect on allograft survival in CCR7−/− mice.

Conclusions.

These results suggest that CCR7-dependent processes support allograft rejection yet are dispensable for the rejection response.

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