Deletion of Spontaneous Rat Liver Allograft Acceptance by Donor Irradiation

Sun, Junhong; McCaughan, Geoffrey W.; Gallagher, N. D.; Sheil, A. G. R.; Bishop, G. Alex

doi:10.1097/00007890-199508000-00004

Cited by 163 publications

(122 citation statements)

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“…Previous studies have shown that TBI of the donor can reduce the number of radiosensitive passenger leukocytes and prevent the induction of tolerance in tol-erogenic rat OLT models [26,29]. This correlates well with our immunofluorescence assay results, which show a markedly reduced number of migrating DA class Ipositive cells in the spleen of the PVG recipient bearing the irradiated DA liver.…”

Section: Discussionsupporting

confidence: 91%

“…The kinetics of the depletion of these cell components appears to be different [S, 291, and one previous study showed that the number of interstitial dendritic cells was undiminished even 24 h after lethal irradiation [S]. Using a naturally tolerogenic combination of rats in OLT, we have demonstrated, as have others [29], that TBI of the donor fails to induce tolerance in these recipients. However, unlike other studies using parking of the liver [27, 291, reconstitution of the irradiated donor with bone marrow cells [31], or injection of cells into the recipient, we reestablished liver-induced tolerance simply by injecting naive donor type spleen cells into the irradiated donor 24 h prior to transplantation [26].…”

Section: Discussionmentioning

confidence: 56%

“…However, unlike other studies using parking of the liver [27, 291, reconstitution of the irradiated donor with bone marrow cells [31], or injection of cells into the recipient, we reestablished liver-induced tolerance simply by injecting naive donor type spleen cells into the irradiated donor 24 h prior to transplantation [26]. Furthermore, our present study shows that splenic "T-cell-enriched" populations may play an important role in the restoration of liver graft acceptance, although we should further investigate the involvement of radio-resistant dendritic cells [8,29] or intrahepatic hematopoietic stem cells [2,20] in the induction of tolerance. This is consistent with other clinical trials and experimental studies that have shown that donor T cells can play a critical role in preventing allogenic marrow graft rejection [18, 191. In the present study, we show that the effect of TBI and/or reconstitution is specific to liver transplantation and cannot be observed in HHT models in which the same donor is used.…”

Section: Discussionmentioning

confidence: 73%

“…It has been demonstrated [22,29,30] that TBI depletes the donor of most passenger leukocytes, including T, B, dendritic, and monocyte/macrophage cells. The kinetics of the depletion of these cell components appears to be different [S, 291, and one previous study showed that the number of interstitial dendritic cells was undiminished even 24 h after lethal irradiation [S].…”

Section: Discussionmentioning

confidence: 99%

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The characterization of reconstituted passenger leukocytes on the induction of tolerance in rat liver transplantation

Chiba

Goto

Shimizu

et al. 1997

Transplant International

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The characterization of reconstituted passenger leukocytes on the induction of tolerance in rat liver transplantation

Chiba

Goto

Shimizu

et al. 1997

Transplant International

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“…In simpler experiments involving only the depletion of organ leukocytes by donor irradiation or other means, both the tolerogenicity and antigenicity of heart 39 , liver 52 and free pancreas islet allografts 53 are abrogated or weakened. The tolerogenicity of liver can be restored by an infusion of donor-strain splenocytes into irradiated donors 24 hours before the organ is removed for transplantation 54 .…”

Section: Cellular and Molecular Mechanismsmentioning

confidence: 99%

The lost chord: microchimerism and allograft survival

et al. 1996

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Recent evidence suggests that passenger leukocytes migrate after organ transplantation and produce persistent chimerism, which is essential for sustained survival of the allografts. Here, Thomas Starzl and colleagues argure that this hematolymphopoietic chimerism provides an important framework for the interpretation of basic and therapeutically oriented transplantataion research.Medawar's characterization of rejection 1 as a host-versus-graft (HVG) reaction (Fig. 1a) was the cornerstone of transplantation immunology. A decade later, this concept was transposed in the context of a graft-versus-host (GVH) reaction (Fig. 1b), in which histoincompatible hematolymphopoietic grafts rejected the immunologically defenseless recipients 2,3 . The resulting assumption that allograft acceptance or rejection could be understood by studying HVG or GVH immunologic responses in isolation led to prompt acceptance of the one-way in vitro tests of immune reactivity as 'minitransplant' surrogates. However, this assumption did not provide a blanket explanation for observations made in animal and human allograft recipients. The one-way paradigmUntil 1959, preparatory donor leukocyte infusion into cytoablated organ recipients was an expected natural extension of the neonatal tolerance model of Billingham, Brent and Medawar 4 and its adult cytoablation analogues 3 . However, when long-term survival of human kidney allografts was accomplished in a few sublethally irradiated recipients without donor leukocyte infusion, and then regularly without cytoreduction under continuous pharmacologic immunosuppression, the need either for chimerism or host preconditioning lost favor.The identification of 'passenger leukocytes' as the primary antigenic component of organs 6,7 led to the belief that their destruction by the host immune system was essential for organ engraftment. When these cells were found to be migratory 8 , including dendritic cells (DCs) 9 , their sensitization effects and presumed elimination at peripheral and intragraft sites was taken for granted. Bone marrow transplantationMajor histocompatibility complex (MHC)-restricted models of acquired tolerance were widely considered to have validated Burnet's prediction that developing lymphocytes could be purged of self-reactive cells before they achieved functional maturity, even following bone marrow transplantation. The alternative possibility that donor and recipient immunecell populations coexisted in neonatally tolerant animals in a mutually nonreactive state while retaining the ability to function collaboratively (e.g. in a joint immune response to infection) was abandoned when no direct experimental support could be found 10 it has since been learned that the outcome in the neonatal tolerance model is highly variable and that a state approaching permanent clonal deletion is uncommon 11 . Recently, it has been shown that the ability of donor-derived leukocyte subsets to proliferate in response to a skin graft challenge was a more critical determinant of neonatal tole...

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Significant role of intragraft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation

et al. 1999

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Graft recurrence of insulin-dependent diabetes mellitus (IDDM) was examined. Islet transplantation or pancreas-alone transplantation excluding the duodenum and peripancreatic lymph nodes was compared with whole pancreaticoduodenal transplantation. A Wistar Furth (WF; RT1(u), RT6.2) to major histocompatibility complex (MHC)-compatible diabetes-prone (DP; RT1(u), RT6.1 gene carrier)-biobreeding (BB) rat transplantation model was used. Only DP recipients that had been transplanted with whole pancreaticoduodenal grafts were free from IDDM recurrence (>60 days postgrafting) when treated with anti-intercellular adhesion moluecule-1 (ICAM)-1/leukocyte function-associated antigen-1 (LFA-1) monoclonal antibodies (mAbs). In the spleen cells of the DP rats that had accepted pancreatic grafts (60 days postgrafting), flow cytometric analysis showed that NKR-P1(+)TCRalphabeta(+) (NKT) cells had proliferated markedly, with the proportion of 12.8 +/- 1.7% in the total splenic T cells, most of which (86.2%) were derived from the donor (RT6.2(+)). By enzyme-linked immunonosorbent assay (ELISA), serum interferon gamma (IFN-gamma) was not detected (<13 pg/ml) in all rats. However, interleukin-4 (IL-4) was detected as 158.8 +/- 28.0 pg/ml in the nonrecurrent DP recipients. These data suggested that to prevent IDDM recurrence in the pancreatic graft, the lymphocytes in the pancreaticoduodenal grafts are necessary. Also, the donor-derived NKT cells might have some immunoregulatory functions with a Th2 deviation.

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Deletion of Spontaneous Rat Liver Allograft Acceptance by Donor Irradiation

Cited by 163 publications

References 0 publications

The characterization of reconstituted passenger leukocytes on the induction of tolerance in rat liver transplantation

The characterization of reconstituted passenger leukocytes on the induction of tolerance in rat liver transplantation

The lost chord: microchimerism and allograft survival

Significant role of intragraft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation

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