Donor-specific immune response after aortic valve allografting in the rat

Abstract

The allospecific immune response in rats to a major histocompatibility complex-disparate aortic valve allograft was investigated using three in vitro assays. In each assay, DA strain (RT-1 a) rats served as allograft recipient and syngeneic donor, Lewis strain (RT-1 1) rats were allogeneic donors, and Buffalo (RT-1 b) rats provided third-party control cells. Mixed lymphocyte cultures using spleen cells demonstrated donor-specific stimulation indices of 3.04 ± 0.44, 4.14 ± 0.62, and 6.32 ± 0.60 at 7, 14, and 28 days, respectively, after aortic valve allografting; 8.19 ± 2.91, 8.51 ± 1.25, and 10.80 ± 0.53 after skin allografting; and 1.84 ± 0.56, 1.82 ± 0.38, and 1.82 ± 0.53 after aortic valve isografting. Limiting dilution analysis of splenocytes showed a donor-specific cytotoxic T lymphocyte precursor frequency at 7, 14, and 28 days of 1:6,853, 1:4,714, and 1:1,964 after aortic valve allografting; 1:4,181, 1:1,611, and 1:1,018 after skin allografting; and 1:14,517, 1:11,882, and 1:10,995 after aortic valve isografting. Flow cytometry detected an increase in the level of donor-specific anti-T cell antibodies in both valve and skin allograft recipients but not in isografted animals. Aortic valve allografting from Lewis into DA rats elicits allospecific cellular and humoral immune responses similar in magnitude to skin allografting but somewhat slower in onset. Investigation of the immune response to aortic allografts in humans is warranted, as donor-specific T cells, antibodies, or both may damage the allograft.