Role of thymus in operational tolerance induction in limb allograft transplant model

被引：37

作者：

Siemionow, Maria ^{[1
]}

Izycki, Dariusz ^{[1
]}

Ozer, Kagan ^{[1
]}

Ozmen, Selahattin ^{[1
]}

Klimczak, Aleksandra ^{[1
]}

机构：

[1] Cleveland Clin Fdn, Dept Plast Surg, Cleveland, OH 44195 USA

来源：

TRANSPLANTATION | 2006年 / 81卷 / 11期

关键词：

operational tolerance; thymus; alpha beta-T-cell-receptor; composite tissue allograft; bone marrow transplantation;

D O I：

10.1097/01.tp.0000209508.37345.82

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: In this study, we evaluated the role of host thymus in tolerance induction in composite tissue allografts (CTA) across major histocompatibility complex (MHC) barrier during a 7-day alpha/beta-T-cell receptor (TCR)/cyclosporine A (CsA) protocol. Materials and Methods: A total of 62 limb allograft transplants were studied. Euthymic (group A) and thymectomized (group B) Lewis recipients (LEW, RT1(1)) received vascularized hind-limb allografts from hybrid Lewis X Brown-Norway (F1), (LBN, RT1(1+n)) donors. Mixed lymphocyte reaction (MLR) and skin grafting assessed donor-specific tolerance in vitro and in vivo, respectively. Flow cytometry determined the efficacy of immunosuppressive protocols and the presence of donor-specific chimerism. Immunocytochemistry revealed the presence of donor-specific cells in the lymphoid organs of recipients. Results: Isograft transplants survived indefinitely. For thymectomized rats, the median survival time (MST) of limb allograft in non-treated recipients was 7 days; monotherapy with alpha/beta-TCR extended MST to 16 days, and CsA therapy extended it to 30 days. Using the alpha beta-TCR/CsA protocol, the MST of allografts was 51 days. For euthymic rats, the MST of limb allograft in non-treated recipients was 7 days; monotherapy with alpha beta-TCR or CsA extended MST to 13 or 22 days, respectively. Treatment with alpha beta-TCR/CsA resulted in indefinite allografts survival (MST=370 days). MLR and skin grafting confirmed donor-specific tolerance in euthymic recipients. Flow cytometry showed stable chimerism in the euthymic rats and transient chimerism in thymectomized limb recipients. Immunoperoxidase staining revealed the persistence of donor-derived cells in the lymphoid tissues of euthymic recipients. Conclusion: We found that the presence of thymus was imperative for the induction of donor-specific tolerance in rat hind-limb composite tissue allografts using a alpha beta-TCR/CsA protocol.

引用

页码：1568 / 1576

页数：9

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