The mechanism of specific prolongation of class I-mismatched skin grafts induced by retroviral gene therapy

European Journal of Immunology
R S MayfieldJ Iacomini

Abstract

In the present study, we examine the mechanism of specific hyporesponsiveness to major histocompatibility complex (MHC) class I-mismatched skin allografts induced by retrovirus-mediated gene transfer of an allogeneic class I gene into syngeneic bone marrow (BM). Using appropriate congenic recombinant mouse strains, we have mapped MHC determinants that are capable of restoring rapid rejection of Kb-bearing skin grafts. Our results indicate that either a single class I or a single class II alloantigen expressed on skin in association with Kb is able to restore the rapid rejection of Kb-mismatched skin grafts. These data suggest that third-party alloantigens expressed on skin in association with Kb abrogate hyporesponsiveness by providing T cell help. Consistent with this interpretation, spleen cells from mice reconstituted with Kb-transduced BM were unable to elicit a significant anti-Kb cytotoxic T lymphocyte response in vitro unless interleukin-2 was added to the culture medium. Skin graft survival was also analyzed on B10. AKM mice thymectomized 3-4 weeks post-reconstitution with Kb-transduced BM. Thymectomy did not result in significantly prolonged survival of B10. MBR skin grafts compared to euthymic controls, suggesting tha...Continue Reading

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Citations

Jun 14, 2000·Transplantation·S GojoC LeGuern
May 12, 2009·Transplantation Reviews·Jerome M LaurenceAlexandra F Sharland
Mar 9, 1999·The Journal of Allergy and Clinical Immunology·C J Hackett, H B Dickler
Nov 18, 2003·Immunological Reviews·Dolca Thomas, Manikkam Suthanthiran
Sep 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chaorui TianJohn Iacomini
Oct 25, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J BagleyJ Iacomini
Aug 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eun-Suk Kang, John Iacomini

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