Histocompatible miniature swine: an inbred large-animal model1

Abstract

Three herds of miniature swine, each homozygous for a different set of alleles at the major histocompatibility complex (MHC), and five intra-MHC recombinant strains, have been reported by the authors' laboratory. One herd (SLAdd) was selected for further inbreeding to achieve a histocompatible line. It has undergone seven additional generations of sequential brother-sister or father-daughter matings (termed G7). To determine the level of histocompatibility of these animals, the authors performed skin and heart transplantation without immunosuppression. In contrast to MHC-matched, minor antigen-mismatched animals that rejected skin in 11 days (median survival time [MST], n=6) and hearts in 35 days (MST, n=4), G7 animals accepted skin for greater than 340 days (>340, >448, and >677 days) and hearts for greater than 265 days (>265 and >269 days). Nevertheless, rejection of second grafts could be induced by sensitization, indicating that weak minor antigens remain, requiring further inbreeding to achieve full histocompatibility. We conclude that G7 animals are sufficiently inbred to accept first set skin and heart grafts indefinitely.

Immunogenicity of umbilical cord tissue–derived cells

“…Preclinical functional studies using human umbilical cord tissue-derived cells (UTCs) are currently in progress, and early results show promise for these UTCs as cellular therapy of retinal disease in animal models. 16 Massachusetts General Hospital (MGH) MHC-defined miniature swine [17][18][19] provide a unique preclinical model to assess immunogenicity of allogeneic UTCs. By approximating donor-recipient mismatch barriers often seen in clinical transplantations, these animals have been used for large animal studies of cellular and solid organ transplantation.…”

Comparative Measurement of Cell-Mediated Immune Responses of Swine to the M and N Proteins of Porcine Reproductive and Respiratory Syndrome Virus

“…Although a few lines of inbred miniature pigs which express the homologous major histocompatibility complex (MHC) molecules exist (6,28), the majority of outbred conventional pigs harbor polymorphic MHC molecules on their cells. That is the primary reason that it has proven difficult to conduct a proper analysis of MHC-restricted T-cell immune responses in pigs immunized with vaccines or infected with the wild-type viruses.…”

Effects of Tolerance Induction on the Actions of Interferon-γ on Porcine Cardiac Allografts

“…Similar to MHC-mismatched recipients, IFN-γ perfusion facilitated rejection in near-syngeneic recipients. Although there were minimal minor antigen differences in G8 animals (5), that may have been unmasked by the IFN-γ perfusion, the rapidity with which heart grafts were rejected suggests that antigen-independent mechanisms were responsible. Likewise, recent studies by El Sawy and colleagues showed that CD8+ memory T cells produced IFN-y within 48 hours after transplantation -and before T cell priming occurred -, which amplified an antigen-independent inflammatory response (7).…”