Induction of xenogeneic neonatal tolerance to transgenic human leukocyte antigen class I grafts

Transplantation
Steven H BorensteinJohn W Chamberlain

Abstract

The immune response against xenografts is vigorous and poorly controlled with conventional immunosuppressants. Therefore, success in xenotransplantation will depend on developing additional approaches such as induction of immunologic unresponsiveness or tolerance. Although classic protocols of neonatal tolerance induction in mice are very tolerogenic in many allogeneic models, they have generally failed in xenogeneic models. The purpose of these studies was to determine whether failure results from an intrinsic property of xenogenic major histocompatibility complex (MHC) molecules themselves or, instead, is caused by some limitation in species-specific molecular interactions distinct from the polymorphic domains of xenogenic MHC molecules. Our approach was to test the ability of lymphoid cells from a transgenic (Tg) mouse donor expressing a xeno-MHC class I molecule encoding the polymorphic alpha1/alpha2 for human leukocyte antigen (HLA)-B7 to induce neonatal tolerance in non-Tg syngeneic C57BL/6 recipients. Because the donor and recipient strains are genetically identical (C57BL/6, H-2b) except for Tg human MHC HLA-B7, any species-specific molecular incompatibility in this mouse anti-human class I xeno-combination that could p...Continue Reading

References

Jun 27, 1992·Lancet·T E StarzlM Trucco
Aug 1, 1996·Immunology Today·F H BachS C Robson
Aug 1, 1997·Scandinavian Journal of Immunology·Y ModiglianiA Coutinho
May 23, 1998·Annual Review of Immunology·H Auchincloss, D H Sachs
Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S H BorensteinJ W Chamberlain
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eve CheukJohn W Chamberlain
Oct 3, 1953·Nature·R E BILLINGHAMP B MEDAWAR
Nov 13, 1956·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·R E BILLINGHAM, L BRENT

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Citations

Dec 16, 2004·Xenotransplantation·Reto M Baertschiger, Leo H Buhler

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