Recipient-Matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine.

Madariaga, Maria Lucia; Michel, Sebastian; Muraglia, G. La; Sihag, Smita; Leonard, DA; Powell, Harrison; Farkash, Evan A.; Colvin, Robert B.; Cetrulo, CL; Huang, Christene A.; Sachs, Daniela; Madsen, Joren C.; Allan, James S.

doi:10.1097/00007890-201407151-01337

Cited by 2 publications

(2 citation statements)

References 18 publications

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“…Moreover, we could show that splenocytes from a third‐party donor had virtually the same effect as donor‐specific splenocytes. This possible bystander effect of cross‐reactive T cells, indicating shared antigens of lung and splenocyte donors, might also explain the protolerogenic effect of recipient matching of the passenger leukocytes . Importantly, administration of subcellular splenocyte‐derived antigen did not improve allograft survival (Figure B) and might potentially even promote rejection through indirect allorecognition as shown by Allan and his group .…”

Section: Discussionmentioning

confidence: 91%

Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine

Avşar

Jansson

Sommer

et al. 2016

American Journal of Transplantation

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Both authors contributed equally to this work. ‡ Both authors share last authorship.Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4 + CD25 high+ T cell frequencies were detected in peripheral blood associated with decreased interferon-c production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with thirdparty splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donorspecific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.

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Section: Discussionmentioning

confidence: 91%

Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine

Avşar

Jansson

Sommer

et al. 2016

American Journal of Transplantation

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“…The unique and often divergent roles of different macrophage populations within a given organ is currently a topic of intense study, but the functional consequence of these differences has not been well defined in the context of solid organ transplantation [100]. In swine, when intrapulmonary passenger leukocytes were MHC-matched to recipients, lung allograft survival was significantly higher than in nonmatched controls [101]. In the human and mouse heart, distinct macrophage populations can be identified based on the expression of CCR2.…”

Section: Macrophagesmentioning

confidence: 99%

Why some organ allografts are tolerated better than others: new insights for an old question

Hull

Bénichou²,

Madsen

2019

Current Opinion in Organ Transplantation

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Purpose of review-There is great variability in how different organ allografts respond to the same tolerance induction protocol. Well known examples of this phenomenon include the protolerogenic nature of kidney and liver allografts as opposed to the tolerance-resistance of heart and lung allografts. This suggests there are organ-specific factors which differentially drive the immune response following transplantation.Recent findings-The specific cells or cell products that make one organ allograft more likely to be accepted off immunosuppression than another are largely unknown. However, new insights have been made in this area recently. Summary-The current review will focus on the organ-intrinsic factors that contribute to the organ-specific differences observed in tolerance induction with a view to developing therapeutic strategies to better prevent organ rejection and promote tolerance induction of all organs.

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Recipient-Matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine.

Cited by 2 publications

References 18 publications

Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine

Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine

Why some organ allografts are tolerated better than others: new insights for an old question

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