Abstract

Previous studies have demonstrated the overwhelming importance of class II matching in determining the fate of vascular allografts in partially inbred miniature swine. When class II loci were genotypically matched, kidneys transplanted between animals differing for class I plus minor antigens were frequently found to induce specific tolerance in otherwise unmanipulated recipients. The major goal of this proposal is to determine the mechanisms by which this tolerance is induced and maintained. Available data indicate that limitation of T-cell help and route of antigen presentation are important factors in these mechanisms.
The specific aims of this proposal are therefore to: (1) examine the immune response of tolerant animals to subsequent skin grafts bearing defined combinations of class I and/or class II differences; (2) determine the effect of further help limitation by administration of cyclosporine A (CsA) during the primary response to selectively mismatched kidney transplants; and (3) study in vitro the activities of graft infiltrating lymphocytes (GILS) isolated from tolerant kidneys.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI031046-02
Application #
3146031
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1991-04-01
Project End
1996-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Fishman, Jay A; Sachs, David H; Yamada, Kazuhiko et al. (2018) Absence of interaction between porcine endogenous retrovirus and porcine cytomegalovirus in pig-to-baboon renal xenotransplantation in vivo. Xenotransplantation 25:e12395
Tasaki, M; Villani, V; Shimizu, A et al. (2016) Role of Bone Marrow Maturity, Insulin-Like Growth Factor 1 Receptor, and Forkhead Box Protein N1 in Thymic Involution and Rejuvenation. Am J Transplant 16:2877-2891
Lee, P W; Hanekamp, J S; Villani, V et al. (2014) Evidence for a gene controlling the induction of transplantation tolerance. Am J Transplant 14:952-9
Scalea, J R; Okumi, M; Villani, V et al. (2014) Abrogation of renal allograft tolerance in MGH miniature swine: the role of intra-graft and peripheral factors in long-term tolerance. Am J Transplant 14:2001-10
Cetrulo Jr, Curtis L; Torabi, Radbeh; Scalea, Joseph R et al. (2013) Vascularized composite allograft transplant survival in miniature swine: is MHC tolerance sufficient for acceptance of epidermis? Transplantation 96:966-74
Hanekamp, John S; Okumi, Masayoshi; Tena, Aseda et al. (2009) Cytoplasmic inheritance of transplantation antigens in animals produced by nuclear transfer. Transplantation 88:30-7
Shimizu, Akira; Yamada, Kazuhiko (2006) Pathology of renal xenograft rejection in pig to non-human primate transplantation. Clin Transplant 20 Suppl 15:46-52
Shimizu, Akira; Colvin, Robert B (2005) Pathological features of antibody-mediated rejection. Curr Drug Targets Cardiovasc Haematol Disord 5:199-214
Mezrich, Joshua D; Benjamin, Louis C; Sachs, Jessica A et al. (2005) Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine. Transplantation 79:1663-73
Wu, Anette; Yamada, Kazuhiko; Baron, Christophe et al. (2004) Detection of regulatory cells as an assay for allograft tolerance in miniature swine. J Heart Lung Transplant 23:210-7

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