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. 2006 Dec;38(10):3268-70.
doi: 10.1016/j.transproceed.2006.10.161.

An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine

T Shoji  1 , H Sahara, A Muniappan, D A Guenther, S L Houser, A C Pujara, M A Bravard, J C Wain, D H Sachs, J C Madsen, J S Allan
Affiliations

An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine

T Shoji et al. Transplant Proc. 2006 Dec.

Abstract

Objectives: The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. We have induced robust tolerance to class I-disparate lung allografts in miniature swine using an intensive 12-day course of tacrolimus. Here, we tested whether a tolerant state can be induced in swine receiving fully mismatched lung allografts.

Methods: Orthotopic left lung allografts were performed using MHC class I-disparate (group 1: n = 3) or fully disparate (group 2: n = 6) donors. The recipients received a 12-day postoperative course of tacrolimus (continuous intravenous infusion; target level = 35-50 ng/mL) as their only immunosuppression.

Results: All swine in group 1 maintained their grafts long term without developing any lesions of chronic rejection (>497, >432, >451 days). These recipients exhibited donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity (CML) and mixed lymphocyte reaction (MLR) assays. In group 2, five of the six recipients maintained their grafts long term (sacrificed on postoperative days 515, 389, 429, 481, and 438 with viable grafts). Isolated lesions of obliterative bronchiolitis were occasionally seen on biopsy, and donor-specific hyporesponsiveness on assays was consistently observed. The remaining recipient rejected its graft on day 103 with histologic findings of obliterative bronchiolitis.

Conclusions: We report long-term graft acceptance without chronic immunosuppression in five of six recipients across a full MHC disparity, albeit with some evidence of obliterative bronchiolitis. These data suggest that the class II disparity inherent in a fully mismatched transplant increases the requirement for tolerance induction.

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Figures

Figure 1
Figure 1
Histological findings of fully mismatched lung allograft (Recipient #15515; POD 347) Mild acute cellular rejection consistent with ISHLT grade 2/4 acute rejection was seen (Figure 1a. H&E stain, x100). No chronic rejection was observed (Figure 1b. Trichrome stain, x200).
Figure 1
Figure 1
Histological findings of fully mismatched lung allograft (Recipient #15515; POD 347) Mild acute cellular rejection consistent with ISHLT grade 2/4 acute rejection was seen (Figure 1a. H&E stain, x100). No chronic rejection was observed (Figure 1b. Trichrome stain, x200).
See this image and copyright information in PMC

References

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