Abstract
Background: Recent studies in mice and patients suggest that posttransplantation induction of autoimmune responses to tissue-specific antigens contributes to the rejection of major histocompatibility complex mismatched allotransplants. The relevance of this phenomenon to the rejection of major and minor histocompatibility-mismatched allografts performed in large-animal models remains to be established. Methods: Miniature swine were immunized with cardiac myosin (CM) in Freund's adjuvant and received heterotopic, minor antigen-mismatched heart transplants. T-cell (proliferation and delayed type hypersensitivity [DTH]) and B-cell (antibody) responses specific to CM were measured. The rejection of heart transplants was assessed histologically. Results: Three of four swine that were immunized with CM before receiving a minor antigen-mismatched heart transplant exhibited potent DTH, T-cell proliferation and antibody responses to CM and rejected their grafts acutely. The fourth swine, which failed to mount a significant DTH response to CM and displayed low and transient anti-CM antibody titers, demonstrated long-term allograft survival. Conclusions: This large-animal study supports the relevance of autoimmunity to CM in the rejection of minor antigen disparate cardiac allotransplants.
Original language | English (US) |
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Pages (from-to) | 1187-1191 |
Number of pages | 5 |
Journal | Transplantation |
Volume | 91 |
Issue number | 11 |
DOIs | |
State | Published - Jun 15 2011 |
Externally published | Yes |
Keywords
- Autoimmunity
- Cardiac myosin
- Heart transplantation
- Swine
ASJC Scopus subject areas
- Transplantation