Tolerance of Lung Allografts Achieved in Nonhuman Primates via Mixed Hematopoietic Chimerism

While the induction of transient mixed chimerism has tolerized MHC‐mismatched renal grafts in nonhuman primates and patients, this approach has not been successful for more immunogenic organs. Here, we describe a modified delayed‐tolerance‐induction protocol resulting in three out of four monkeys ac...

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Bibliographic Details
Published in:American journal of transplantation 2015-08, Vol.15 (8), p.2231-2239
Main Authors: Tonsho, M., Lee, S., Aoyama, A., Boskovic, S., Nadazdin, O., Capetta, K., Smith, R.‐N., Colvin, R. B., Sachs, D. H., Cosimi, A. B., Kawai, T., Madsen, J. C., Benichou, G., Allan, J. S.
Format: Article
Language:English
Subjects:
Animal models
Animals
basic (laboratory) research/science
Chimerism
Hematopoiesis
Lung Transplantation
lung transplantation/pulmonology
Macaca fascicularis
nonhuman primate
Primates
tolerance
translational research/science
Transplantation, Homologous
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Summary:While the induction of transient mixed chimerism has tolerized MHC‐mismatched renal grafts in nonhuman primates and patients, this approach has not been successful for more immunogenic organs. Here, we describe a modified delayed‐tolerance‐induction protocol resulting in three out of four monkeys achieving long‐term lung allograft survival without ongoing immunosuppression. Two of the tolerant monkeys displayed stable mixed lymphoid chimerism, and the other showed transient chimerism. Serial biopsies and post‐mortem specimens from the tolerant monkeys revealed no signs of chronic rejection. The tolerant recipients also exhibited T cell unresponsiveness and a lack of alloantibody. This is the first report of durable mixed chimerism and successful tolerance induction of MHC‐mismatched lungs in primates. The authors achieve nonhuman primate lung allograft tolerance using a mixed‐hematopoietic chimerism strategy.
ISSN:1600-6135
1600-6143
DOI:10.1111/ajt.13274