Weiss M J, Guenther D A, Mezrich J D, Sahara H, Ng C Y, Meltzer A J, Sayre J K, Cochrane M E, Pujara A C, Houser S L, Sachs D H, Rosengard B R, Allan J S, Benichou G, Madsen J C
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Am J Transplant. 2009 Jan;9(1):105-13. doi: 10.1111/j.1600-6143.2008.02494.x.
We studied the effects of indirect allorecognition on the induction and maintenance phases of tolerance in miniature swine cotransplanted with heart and kidney allografts. MHC class I-mismatched heart and kidney grafts were cotransplanted in recipients receiving CyA for 12 days. Recipients were unimmunized or immunized with a set of donor-derived or control third-party MHC class I peptides either 21 days prior to transplantation or over 100 days after transplantation. T-cell proliferation, delayed type hypersensitivity reaction (DTH) and antibody production were assessed. All animals injected with donor MHC class I peptides developed potent indirect alloresponses specific to the immunizing peptides. While untreated recipients developed stable tolerance, all animals preimmunized with donor allopeptides rejected kidney-heart transplants acutely. In contrast, when peptide immunization was delayed until over 100 days after kidney-heart transplantation, no effects were observed on graft function or in vitro measures of alloimmunity. Donor peptide immunization prevented tolerance when administered to recipients pre transplantation but did not abrogate tolerance when administered to long-term survivors post transplantation. This suggests that the presence of T cells activated via indirect allorecognition represent a barrier to the induction but not the maintenance of tolerance.
我们研究了间接同种异体识别对同时移植心脏和肾脏异体移植物的小型猪耐受诱导和维持阶段的影响。将MHC I类不匹配的心脏和肾脏移植物同时移植到接受环孢素（CyA）治疗12天的受体中。受体在移植前21天或移植后100多天未进行免疫或用一组供体来源的或对照第三方MHC I类肽进行免疫。评估了T细胞增殖、迟发型超敏反应（DTH）和抗体产生。所有注射供体MHC I类肽的动物都产生了针对免疫肽的强烈间接同种异体反应。未经治疗的受体形成了稳定的耐受，而所有用供体同种异体肽预免疫的动物都急性排斥了肾脏-心脏移植。相反，当肽免疫延迟到肾脏-心脏移植后100多天时，对移植物功能或同种免疫的体外测量没有观察到影响。供体肽免疫在移植前给予受体时会阻止耐受，但在移植后给予长期存活者时不会消除耐受。这表明通过间接同种异体识别激活的T细胞的存在是耐受诱导的障碍，但不是耐受维持的障碍。
