Co-Transplantation of Donor-Derived Hepatocytes Induces Long-Term Tolerance to Cardiac Allografts in a Rat Model1

Yoo-Ott, Kyoung-Ae; Schiller, H.; Fändrich, F.; Oswald, Hanno; Richter, K.; Xhu, Xiao-Feng; Kampen, Willm Uwe; Krönke, Martin; Zavazava, Nicholas

doi:10.1097/00007890-200006270-00012

Cited by 17 publications

(10 citation statements)

References 35 publications

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“…In similar rodent models, liver co-transplantation has been shown to prevent the rejection of skin allografts (159,173) and to reverse acute rejection of cardiac allografts (174). The protective effect of liver allografts may not require transplantation of the whole organ, as demonstrated by a rat study in which infusion of donor hepatocytes, but not hepatic leukocytes, into the portal vein prevented the rejection of cardiac allografts (175). In the clinical setting, liver co-transplantation has been shown to have a protective effect on small bowel (176), heart (177), and combined heart and lung (178) transplantation.…”

Section: The Liver Effectmentioning

confidence: 99%

The role of the graft in establishing tolerance

Karim¹

2002

Front Biosci

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At the present time, clinical solid organ transplantation continues to rely on the use of non-specific immunosuppressive protocols in order to prevent graft rejection. However, these regimens bring with them complications related both to the global immunosuppression that they cause, and to toxicity related to individual drugs. The pursuit of protocols that will allow graft-specific tolerance thus remains a major goal of research both in animal models and in clinical practice. There is evidence that the graft itself may play an active part in establishing and maintaining donor-specific hyporesponsiveness and ultimately tolerance; the aim of this review is to analyze this role in more detail.

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Section: The Liver Effectmentioning

confidence: 99%

The role of the graft in establishing tolerance

Karim¹

2002

Front Biosci

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“…They surmised that mechanisms in the liver graft itself were involved in tolerance induction. Yoo‐Ott et al12 reported that donor‐derived hepatocytes protected cardiac allografts from acute and chronic rejection in rat. A chimeric liver probably has the ability to stimulate T cells via the indirect pathway 10.…”

Section: Discussionmentioning

confidence: 99%

“…In tissue and organ transplantation, the importance of the direct pathway in graft rejection has been stressed,6–8 and the indirect pathway has been suggested to be more important in graft rejection 9, 10. In liver transplantation, however, hepatocytes exert an immunologic effect on graft acceptance11 and appear to regulate both the direct and indirect pathways 12. Recent investigations have shown the role of the passenger leukocyte genotype in the rejection and acceptance of rat liver allografts 13.…”

mentioning

confidence: 99%

Cytotoxic T-cell elimination during anti-CD4-induced rat liver acceptance and rapid replacement of functional graft antigen-presenting cells

Usui

Yamaguchi

et al. 2004

Liver Transpl

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In previous studies, we showed that primed T cells were eliminated in long-term survival Wistar Furth (WF) recipient rats with spontaneously accepted Lewis (LEW) liver graft and that the grafted liver lost the ability to elicit rejection reaction early after liver transplantation. We hypothesized that the same phenomenon may be observed in tolerant animals after immunosuppression in a rejector rat strain combination (WF3 LEW). Furthermore, we proposed the repopulation of liver allograft with host antigen -presenting cells rapidly after transplantation. Recipient LEW rats that underwent anti-CD4 therapy accepted the WF liver allografts after a transient rejection reaction. In tolerant animals, alloreactive CD8 T cell precursors were present, but primed T cells were absent. D eletional mechanisms of effector T cells may play a role in transplantation tolerance. 1,2 We previously have shown that treatment with anti-CD4 monoclonal antibody (mAb) induced heart allograft tolerance but not skin allograft acceptance in the Wistar Furth (WF) to Lewis (LEW) rat strain combination. We also examined the differences in cellular responses between heart-bearing and skin-rejected hosts. 3 Our results showed that primed T cells were present in anti-CD4-treated WF skin-rejected LEW rats and that the secondary donor heart and skin grafts resulted in accelerated rejection in the hosts, in sharp contrast to anti-CD4-treated WF heart-bearing LEW rats. That is, no primed T cells were present, and the survival of secondary donor grafts was prolonged in the heart-bearing hosts.In rat liver transplantation, the grafted liver itself has been reported to be involved in immune tolerance using a retransplantation model, and the Kupffer cell population in the graft at the time of retransplantation has been shown to be almost completely of recipient origin. 4 Because it is conceivable that the chimeric retransplanted liver is associated with reduced immunogenicity, 5 the establishment of tolerance may be caused by the pathway of indirect allorecognition. In tissue and organ transplantation, the importance of the direct pathway in graft rejection has been stressed, 6 -8 and the indirect pathway has been suggested to be more important in graft rejection. 9,10 In liver transplantation, however, hepatocytes exert an immunologic effect on graft acceptance 11 and appear to regulate both the direct and indirect pathways. 12 Recent investigations have shown the role of the passenger leukocyte genotype in the rejection and acceptance of rat liver allografts. 13 They noted that recipient-type passenger leukocytes in the hepatic allograft were involved in graft acceptance in the rejector rat strain combination.In this study, we used an anti-CD4 induced liver acceptance model. We observed that primed T cells were absent in tolerant animals overcoming acute rejection responses and that functional donor antigen-presenting cells (APCs) were almost completely replaced by those of the recipient genotype within the graft by

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“…Çà â³äñóòíîñò³ îñòð³âö³â ï³äøëóíêîâî¿ çàëîçè àãðåãàòè ãåïàòîöèò³â äåãåíåðóâàëè, íå-çâàaeàþ÷è íà çàñòîñóâàííÿ öèêëîñïîðèíó À, çà-ëèøàþ÷è ëèøå òîíêèé øàð êë³òèí, ùî áåçïîñå-ðåäíüî ïðèëÿãàëè äî íèðêîâî¿ ïàðåíõ³ìè. Öå Êë³í³÷íà åíäîêðèíîëîã³ÿ òà åíäîêðèííà õ³ðóðã³ÿ 1(42) 2013 ÎÃËßÄÈ ñâ³ä÷èòü ïðî ìîaeëèâó ðîëü òðîô³÷íèõ ÷èííèê³â, ÿê³ ëîêàëüíî âèâ³ëüíÿþòüñÿ ç îñòð³âö³â ï³äøëóí-êîâî¿ çàëîçè [104]. Êîìá³íîâàíà àëîòðàíñïëàí-òàö³ÿ ãåïàòîöèò³â òà îñòð³âö³â ï³äøëóíêîâî¿ çà-ëîçè ó ñåëåç³íêó òàêîae ñïðèÿëà òðèâàë³øîìó âèaeèâàííþ êë³òèí (ïîíàä 1 ì³ñÿöü) ïîð³âíÿíî ç ïîîäèíîêèìè òðàíñïëàíòàòàìè ãåïàòîöèò³â [105].…”

Section: êë³í³÷íà åíäîêðèíîëîã³ÿ òà åíäîêðèííà õ³ðóðã³ÿ 1(42) 2013unclassified

Combined xenotransplantation as a method of prolonging the viability and function of the graft in the treatment of various forms of hypocorticism

Ларін¹,

Анастасій²,

Гирявенко³

et al. 2013

CE&ES

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Co-Transplantation of Donor-Derived Hepatocytes Induces Long-Term Tolerance to Cardiac Allografts in a Rat Model1

Cited by 17 publications

References 35 publications

The role of the graft in establishing tolerance

The role of the graft in establishing tolerance

Cytotoxic T-cell elimination during anti-CD4-induced rat liver acceptance and rapid replacement of functional graft antigen-presenting cells

Combined xenotransplantation as a method of prolonging the viability and function of the graft in the treatment of various forms of hypocorticism

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