Trafficking of host- and donor-derived dendritic cells in rat cardiac transplantation: allosensitization in the spleen and hepatic nodes.

Abstract

Kinetics and role of host and donor dendritic cells (DCs) in transplantation immunity are still ill-defined. Using a rat cardiac transplantation model, we studied DC trafficking and sites for allosensitization. Host and donor DCs were defined as host- or donor-type class II major histocompatibility complex antigen single-positive cells by double-immunostaining. Proliferative response of both donor and host cells were also analyzed. Host DCs were recruited to the graft soon after transplantation. These cells represented definitive precursors because of high labeling index by a continuous bromodeoxyuridine infusion, their small round shape, and their putative bone marrow origin. Donor interstitial DCs showed a significant self-replicating capability. Both recruited host DCs in a regraft experiment and donor DCs preferentially performed blood-borne migration to the T-cell area of host spleen. Furthermore, they also migrated to the T-cell area of hepatic lymph nodes after executing the sinusoids-lymph translocation as a novel pathway for these DCs. Selectively at their migration sites, a strong T-cell proliferative response occurred, which preceded that in the graft tissues. Removal of spleen and hepatic lymph nodes significantly prolonged the mean graft survival time. We conclude that allogeneic heart transplantation induces the recruitment of host DC precursors to the graft tissues and the blood-borne migration of both recruited host and donor DCs to the host spleen and hepatic nodes where effector cells are predominantly sensitized.