A study of graft versus host disease using bile duct implants under the kidney capsule
- Author(s)
- Hardy, CL; Morahan, G; Bhathal, PS;
- Details
- Publication Year 2000-02,Volume 20,Issue #1,Page 16-26
- Journal Title
- LIVER
- Publication Type
- Journal Article
- Abstract
- Aims/Background: Graft versus host disease (GVHD) following histoincompatible bone marrow transplantation may be modelled experimentally using irradiated metallothionein promoter-H-2K(b) transgenic mice (MET-Kb mice), reconstituted with syngeneic non-transgenic spleen and lymph node (LN) cells. In this model, inflammation peaks at 3 weeks post-reconstitution, but resolves by 3 months, and is focussed on portal tracts and bile ducts (BD). The aim of this study was to determine if transgene-expressing hepatocytes play a role in the immune response why portal tracts are selectively targeted, and which cell types are involved. Methods: Intrahepatic ED (IHBD) with attached hepatocytes. or extrahepatic ED (EHBD) devoid of hepatocytes, were isolated from MET-Iib mice and implanted under the kidney capsule of transgenic (syngeneic) and congenic (allogeneic) mice. Three weeks post-implantation, ED were scored histologically for rejection or survival, and stained for various cell-surface molecules. Results: Generally, IHBD survived better than EHBD, and T cells were the predominant infiltrating cell type ill both implants. Both types of implants undergoing rejection expressed intercellular adhesion molecule-1 (ICAM-1) and leukocyte function antigen-1 (LFA-I) at high density; ED and the underlying kidney parenchyma also expressed class I and II major histocompatibility complex (MHC). Conclusions. The rejection of both groups of implants by congenic recipients suggests that ED from MET-Kb mice express the transgene, but the reason for the selective targeting of portal tracts rather than transgene-expressing hepatocytes remains unclear. One possible explanation is that dendritic cells/antigen-presenting cells (DC/APC) in portal tracts, which express high levels of MHC and co-stimulatory molecules, are the primary targets, and that ED are infiltrated and destroyed as 'bystanders'.
- Publisher
- MUNKSGAARD INT PUBL LTD
- Keywords
- MAJOR HISTOCOMPATIBILITY COMPLEX; INTERCELLULAR-ADHESION MOLECULE-1; HUMAN-LIVER GRAFTS; PRIMARY BILIARY-CIRRHOSIS; CLASS-I; TRANSGENIC MICE; ANTIGEN EXPRESSION; HEPATIC GRAFT; REJECTION; CELLS
- Publisher's Version
- https://doi.org/10.1034/j.1600-0676.2000.020001016.x
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-02-01 12:00:00