Soluble donor MHC class I gene transfer to thymus promotes allograft survival in a high-responder heart transplant model.
Thymic selection of self and non-self-reactive lymphocytes is a process that may be targeted to induce donor-specific immunologic unresponsiveness in organ transplantation. In the present study, gene transfer was used to preexpose the recipient thymus to soluble donor-specific MHC class I molecules prior to heart transplantation in the high-responder ACI (RT1a) to Lewis (RT1l) rat strain combination. Specifically, cultured Lewis hepatocytes were transfected with DNA encoding a secreted form of the donor allo-MHC class I antigen, RT1.Aa. Seven days prior to ACI heart transplantation, genetically altered recipient-strain hepatocytes were injected into the thymus of Lewis recipients which also received a dose of antilymphocyte serum (ALS). Results showed that treatment with both ALS and soluble donor MHC-expressing hepatocytes prolonged transplant survival time by twofold, compared to injection of control hepatocytes and ALS. Therefore, intrathymic gene therapy delivery of soluble donor MHC molecules may be useful for promoting allograft survival in heart transplantation.
Geissler
E K
EK
University of South Alabama, Department of Clinical Laboratory Sciences, Mobile 36604-3273, USA. egeissle@jaguar1.usouthal.edu
Scherer
M N
MN
Graeb
C
C
D000818:Animals; D017690:Cell Transplantation; D002478:Cells, Cultured; D005805:Genes, MHC Class I; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D022781:Hepatocytes / Q000166:cytology / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D013950:Thymus Gland; D014162:Transfection / Q000379:methods*; D014184:Transplantation, Homologous