Inhibition of complement, evoked antibody, and cellular response prevents rejection of pig-to-primate cardiac xenografts

被引:55
作者
Davis, EA
Pruitt, SK
Greene, PS
Ibrahim, S
Lam, TT
Levin, JL
Baldwin, WM
Sanfilipo, F
机构
[1] JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205
[2] JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205
[3] DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710
[4] T CELL SCI INC,NEEDHAM,MA
关键词
D O I
10.1097/00007890-199610150-00022
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Complement (C) inhibition alone using a recombinant soluble form of complement receptor type 1 (sCR1) prevents hyperacute rejection but not subsequent irreversible accelerated acute rejection of dis cordant pig-to-cynomolgus monkey cardiac xenografts, which occurs within 1 week. To inhibit accelerated acute rejection, which is associated with a rise in serum xenoreactive antibody (Ab) and a cellular infiltrate, triple therapy with standard immunosuppressive agents (cyclosporine, cyclophosphamide, and steroids [CCS]) was combined with continuous C inhibition using sCR1. Each of two monkeys that re ceived sCR1 + CCS showed minimal evidence of rejection when killed on days 21 and 32 in comparison to a monkey that received sCR1 + subtherapeutic CCS (rejected at 11 days) and a control that received CCS alone (rejected at 38 min). Prolonged xenograft survival was associated with low Ab levels and a minimal cellular infiltrate, suggesting that combined inhibition of C, xenoreactive Ab responses, and cellular immunity may be a useful approach in overcoming the immune barriers to discordant xenotransplantation.
引用
收藏
页码:1018 / 1023
页数:6
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