Presensitization accelerates allograft arteriosclerosis.
Transplant arteriosclerosis is the major factor influencing allograft survival after the first year posttransplantation. The host's immunologic response is one of the principal effectors responsible for the constitution of this vascular wall lesion, but the effector pathway and the factors influencing the immune injury are not clear. In a rat abdominal aortic allograft model, we used a skin priming method to study the influence of sensitization on the occurrence of vascular wall lesions. Primed rats developed transplant arteriosclerosis lesions involving medial decellularization and intimal proliferation before the 21st day, whereas naive animals had the same lesions at 2 months posttransplantation. A significant difference between primed and naive rats was found for medial thickness (48.00 +/- 2.85 microm versus 79.34 +/- 2.55 microm, P<0.001) and smooth muscle cell content (160 +/- 28 cell/mm versus 466 +/- 19 cell/mm, P<0.001) at 21 days posttransplantation, and intimal hyperplasia was seen in primed animals at that time, whereas it was not observed in naive rats until the 60th day. The immune profile in naive and primed animals was different. The immune cells infiltrating the arterial wall in naive rats, were principally macrophages and CD8+ T-lymphocytes. No Ig or complement deposition was detected. IgG and complement activated fraction were present in the media of primed animals as early as the fifth day posttransplantation and CD4+ T lymphocytes were the dominant immune cell population. In conclusion, sensitization influences the immune mechanisms responsible for the development of transplant arteriosclerosis and alters the rate of its evolution.
Kolb
F
F
U367 INSERM, Paris, France.
Heudes
D
D
Mandet
C
C
Plissonnier
D
D
Osborne-Pellegrin
M
M
Bariety
J
J
Michel
J B
JB
D000818:Animals; D001012:Aorta, Abdominal / Q000276:immunology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D003165:Complement System Proteins / Q000378:metabolism; D006084:Graft Rejection / Q000473:pathology; D007074:Immunoglobulin G / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000009:adverse effects*
D007074:Immunoglobulin G; D003165:Complement System Proteins