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

Transplantation. 2001 Jun 27;71(12):1806-15. doi: 10.1097/00007890-200106270-00017.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cell Division
  • Cell Movement
  • Dendritic Cells / metabolism
  • Dendritic Cells / physiology*
  • Graft Survival
  • Heart Transplantation*
  • Immunization
  • Isoantigens / immunology
  • Kinetics
  • Liver / immunology
  • Liver / pathology
  • Lymph Node Excision
  • Lymph Nodes / pathology
  • Male
  • Myocardium / pathology
  • Rats
  • Rats, Inbred BUF
  • Rats, Inbred Strains
  • Spleen / immunology
  • Spleen / pathology
  • Splenectomy
  • T-Lymphocytes / pathology
  • Tissue Donors*

Substances

  • Biomarkers
  • Isoantigens