Regulatory Tolerance Across a Full MHC Barrier Is More Robust Than Tolerance Across a Class I MHC Disparity Alone
Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Meeting: 2015 American Transplant Congress
Abstract number: 246
Keywords: MHC class I, MHC class II, Tolerance
Session Information
Session Name: Concurrent Session: Transplant Tolerance: Animal Models I
Session Type: Concurrent Session
Date: Monday, May 4, 2015
Session Time: 2:15pm-3:45pm
Presentation Time: 3:15pm-3:27pm
Location: Room 121-C
Background: We previously demonstrated that tolerance of hearts and/or kidneys achieved across a class I MHC mismatch with 12 days of CyA can be abrogated by challenge with skin grafts or class I peptide immunization. In this study, we investigated whether the state of tolerance of class I antigens achieved across a full MHC mismatch is quantitatively or qualitatively different from that induced across a class I MHC mismatch alone.
Methods: Miniature swine that were tolerant of heart and/or kidney allografts long-term across class I or full MHC disparities underwent class I peptide immunization or placement of skin grafts expressing donor class I and 3rd party class II antigens. Animals tolerant of heart and kidney allografts across a full MHC mismatch underwent kidney allograftectomy to prior to skin grafting (Group 1, n=3) or heart and kidney allograftectomy prior to peptide immunization (Group 2, n=3). Animals tolerant of heart and kidney allografts across a class I MHC mismatch underwent kidney allograftectomy prior to skin grafting (Group 3, n=4). Animals tolerant of kidney allografts across a class I MHC mismatch underwent kidney allograftectomy prior to peptide immunization (Group 4, n=2).
Results: Challenge skin grafting resulted in rejection of heart allografts within 50 days in animals tolerant across a class I MHC mismatch (Group 3); in contrast, animals tolerant across a full MHC mismatch maintained long-term heart allograft survival >100 days after skin grafting (Group 1). Class I peptide immunization resulted in return of anti-donor responsiveness by CML, IgG alloantibody production, and rejection of a subsequently placed donor-matched kidney allograft in animals tolerant across a class I MHC mismatch (Group 4) but not in animals tolerant across a full MHC mismatch (Group 2).
Conclusion: Once established, the state of tolerance to class I antigens induced across a full MHC mismatch appears to be more stable than that induced across an isolated class I MHC mismatch. The addition of a class II disparity in a full MHC mismatch thus appears to lead to the generation of more robust down-regulation of class I-specific alloreactivity.
To cite this abstract in AMA style:
Madariaga M, Michel S, II GLaMuraglia, O'Neil M, Orent W, Villani V, Sekijima M, Farkash E, Colvin R, Allan J, Yamada K, Madsen J, Sachs D. Regulatory Tolerance Across a Full MHC Barrier Is More Robust Than Tolerance Across a Class I MHC Disparity Alone [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/regulatory-tolerance-across-a-full-mhc-barrier-is-more-robust-than-tolerance-across-a-class-i-mhc-disparity-alone/. Accessed May 17, 2025.« Back to 2015 American Transplant Congress