Rganspecific variations in allograft rejection and tolerance, focusing on methods we may harness the tolerogenicity of kidney allografts to attain longterm, immunosuppressionfree survival of additional stringent heart allografts.ORGANSPECIFIC Differences IN REJECTIONTable .Proportion of liver, kidney, and heart allografts surviving .d in totally MHC disparate murine recipients Strain mixture Liver Kidney HeartCBL into BALBc (Hb) (Hd) BALBc into CBA (Hd) (Hk) CBL into CH HeN (Hb) (Hk) Recipients received no treatment; n recipientsgroup (from Zhang et al).By far the most extreme examples of organspecific variations in transplantation are experimental models in which kidney and liver allografts are accepted spontaneously (without the need of the use of immunosuppression), whereas other allografts like heart, intestine, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21466250 and skin Tetrabenazine (Racemate) site transplanted across the same MHC barrier are rejected acutely (Russell et al.; Dahmen et al.; Qian et al.; Zhang et al.; Bickerstaff et al.; Cook et al.; Li et al.; Miyajima et al.; Wang et al).Zhang et al. compared liver, kidney, and heart transplantation in three distinct MHC disparate mouse strain combinations without having remedy.The differences inside the patterns of rejection involving organs have been remarkably constant (Table).The majority of liver allografts in each strain combination have been spontaneously accepted long-term, whereas heart grafts transplanted across identical histocompatibility barriers have been all rejected in , d.The pattern of kidney allograft rejection was mixed, with of organs surviving long term (Table) (Zhang et al).Our results (Madsen et al.; Miyajima et al) and other individuals (Bickerstaff et al.; Cook et al.; Wang et al) in mice help the fact that kidney allografts possess a drastically prolonged survival compared with heart allografts transplanted across the exact same MHC barrier.Organspecific variations in rejection responses extend to human transplantation.For instance, the graft halflife for heart allografts is yr (Stehlik et al), whereas the graft halflife for lung allografts is only yr (Christie et al).Therefore, the organspecific differences in transplantation have clinical significance and deserve further study.ORGANSPECIFIC Variations IN TOLERANCE INDUCTIONwww.perspectivesinmedicine.orgOur laboratory has compared the immunobiology of heart, kidney, and lung transplantation in MHC inbred miniature swine (Madsen).These big animals provide the only preclinical model in which organ transplants may be performed across the exact same histocompatibility barrier reproducibly (Sachs).In brief, when porcine recipients were transplanted with MHC class I disparate hearts and treated with d of CyA, they all rejected within d and showed the florid intimal proliferation of CA V on necropsy (Madsen et al).In contrast, when swine had been transplanted with class I disparate kidney allografts and treated with all the exact same course of CyA, they all became tolerant to donor antigen and maintained great renal function long term, in some situations for .yr (Fig) (Rosengard et al).The survival of lungs transplanted across precisely the same class I barrier with d of CyA were in in between that of hearts and kidneys, with graft survival ranging from to .d and twothirds establishing obliterative bronchiolitis (Allan et al).A similarCite this article as Cold Spring Harb Perspect Med ;aM.Tonsho et al. Graft survival Postoperative daysFigure .Heart versus kidney transplantation in MHC class I disparate swine treated having a d course of CyA.www.perspectivesinmedic.
