Related Experiment Video
Updated: Oct 30, 2025
Murine Cervical Aortic Transplantation Model using a Modified Non-Suture Cuff Technique
Published on: November 2, 2019
Donor MHC and adhesion molecules in transplant arteriosclerosis
1Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Insights
Donor vessel molecules impact transplant arteriosclerosis. Intercellular adhesion molecule-1 (ICAM-1) and MHC II promote it, while MHC I may protect grafts by reducing smooth muscle cell accumulation.
Area of Science:
- Immunology
- Transplantation Biology
- Vascular Biology
Background:
- Transplant-associated arteriosclerosis (TAA) is a major cause of long-term graft failure.
- The role of donor-derived molecules in TAA pathogenesis is not fully understood.
- Molecules like MHC and adhesion molecules are critical in immune responses and cell interactions.
Purpose of the Study:
- To investigate the contribution of donor vasculature-expressed MHC and adhesion molecules to TAA.
- To elucidate the specific roles of MHC I, MHC II, P-selectin, and ICAM-1 in TAA development.
Main Methods:
- Carotid artery allografts from mutant mice deficient in specific molecules were transplanted into immunocompetent recipients.
- Mice strains included deficiencies in MHC I, MHC II, both MHC I and II, P-selectin, and ICAM-1.
- Neointima formation and cellular infiltration (CD4+ T cells, alpha-actin+ SMCs) were quantified.
Main Results:
- Absence of ICAM-1, MHC II, or both MHC I/II in donor arteries reduced neointima formation by 52%, 33%, and 38%, respectively, mainly by decreasing smooth muscle cell (SMC) accumulation.
- P-selectin deficiency did not alter neointima formation; combined P-selectin and ICAM-1 deficiency showed similar results to ICAM-1 deficiency alone.
- MHC I deficiency in donor arteries increased neointima formation by 52%, accompanied by a 2.8-fold increase in CD4+ T cells and a twofold increase in alpha-actin+ SMCs.
Conclusions:
- Donor vessel wall ICAM-1 and MHC II molecules promote transplant-associated arteriosclerosis.
- Donor-derived MHC I molecules may exert a protective effect against TAA.
- Targeting these donor molecules could offer therapeutic strategies to improve graft survival.
Abstract:
Transplant-associated arteriosclerosis remains an obstacle to long-term graft survival. To determine the contribution to transplant arteriosclerosis of MHC and adhesion molecules from cells of the donor vasculature, we allografted carotid artery loops from six mutant mouse strains into immunocompetent CBA/CaJ recipients. The donor mice were deficient in either MHC I molecules or MHC II molecules, both MHC I and MHC II molecules, the adhesion molecule P-selectin, intercellular adhesion molecule (ICAM)-1, or both P-selectin and ICAM-1. Donor arteries in which ICAM-1, MHC II, or both MHC I and MHC II were absent showed reductions in neointima formation of 52%, 33%, and 38%, respectively, due primarily to a reduction in smooth muscle cell (SMC) accumulation. In P-selectin-deficient donor arteries, neointima formation did not differ from that in controls. In donor arteries lacking both P-selectin and ICAM-1, the size of the neointima was similar to that in those lacking ICAM-1 alone. In contrast, neointima formation increased by 52% in MHC I-deficient donor arteries. The number of CD4-positive T cells increased by 2.8-fold in MHC I-deficient arteries, and that of alpha-actin-positive SMCs by twofold. These observations indicate that ICAM-1 and MHC II molecules expressed in the donor vessel wall may promote transplant-associated arteriosclerosis. MHC I molecules expressed in the donor may have a protective effect.
Related Concept Videos
01:40Cell-mediated Immune Responses
01:28Kidney Transplant I: Introduction
01:24Tissue Transplantation
The Biology of Tissue Transplantation
The biology of tissue transplantation hinges on the Major Histocompatibility Complex (MHC) molecules. These molecules...