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. 2009 Jan-Feb;41(1):429-30.
doi: 10.1016/j.transproceed.2008.08.147.

Comparison of lung and kidney allografts in induction of tolerance by a mixed-chimerism approach in cynomolgus monkeys

A Aoyama  1 , C Y Ng, T M Millington, S Boskovic, T Murakami, J C Wain, S L Houser, J C Madsen, T Kawai, J S Allan
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Comparison of lung and kidney allografts in induction of tolerance by a mixed-chimerism approach in cynomolgus monkeys

A Aoyama et al. Transplant Proc. 2009 Jan-Feb.

Abstract

Background: We have previously reported the successful induction of renal allograft tolerance in non-human primates using a nonmyeloablative conditioning regimen to produce a mixed-chimeric state in the recipient. In the present study, we applied this same technique to lung allotransplantation in cynomolgus monkeys.

Methods: Nine pairs of fully major histocompatibility complex (MHC)-mismatched cynomolgus monkeys were used. The conditioning regimen consisted of total body irradiation, thymic irradiation, and antithymocyte globulin. The recipients underwent lung and bone marrow transplantation, followed by anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine. The regimen included anti-CD8 mAb in the last 5 recipients and alpha 1-antitripsin in the last 3 recipients. The results were compared with 8 recipients that received kidney allografts using the same regimen.

Results: Transient chimerism developed in all lung recipients, as was previously seen in the kidney recipients. Nonetheless, the lung recipients rejected their allografts significant earlier than the kidney recipients (P < .01).

Conclusions: Despite the successful induction of mixed chimerism in recipients of fully MHC-mismatched lung allografts, we have not observed long-term graft survival, as has been seen in an analogous kidney model. Strategies to overcome this problem include organ-specific modifications of the transplant regimen.

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