Induction of specific tolerance by intrathymic injection of recipient muscle cells transfected with donor class I major histocompatibility complex.

Published

Journal Article

Induction of tolerance to allogeneic MHC antigens has been a goal in the field of transplantation because it would reduce or eliminate the need for generalized immunosuppression. Although encouraging results have been obtained in experimental models by exposing recipient thymus to donor cells before transplantation, donor cells are not typically available at that time, and the donor antigens responsible for the effect are poorly defined. In the present study, thymic tolerance was demonstrated without using donor cells. Recipient thymus was injected before transplantation with autologous myoblasts and myotubes that were genetically modified to express allogeneic donor-type MHC class I antigen. Donor-specific unresponsiveness was induced to a completely MHC-disparate liver transplant and to a subsequent donor-type cardiac allograft, but not a third-party allograft. In vitro, recipient CTL demonstrated a 10-fold reduction in killing of donor cells, but not of third-party cells. Our results demonstrate: (1) that recipient muscle cells can be genetically engineered to induce donor-specific unresponsiveness when given intrathymically, and (2) transfected recipient cells expressing only donor MHC class I antigen can induce tolerance to a fully allogeneic donor.

Full Text

Duke Authors

Cited Authors

  • Knechtle, SJ; Wang, J; Jiao, S; Geissler, EK; Sumimoto, R; Wolff, J

Published Date

  • April 15, 1994

Published In

Volume / Issue

  • 57 / 7

Start / End Page

  • 990 - 996

PubMed ID

  • 8165719

Pubmed Central ID

  • 8165719

International Standard Serial Number (ISSN)

  • 0041-1337

Language

  • eng

Conference Location

  • United States