Pre-transplant analysis of accommodation in donor pigs

William E. Beschorner, C. Carson Shearon, Tianyu Yang, Alan N. Langnas, Scott C. Thompson, Yong Zhao, Kenneth L. Franco, Stanley J. Radio, Debra L. Sudan

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Accommodation could lead to xenograft acceptance without the need for severe immune suppression. Generally graft accommodation is appreciated in the sensitized recipient, after transplantation. By inducing accommodation in chimeric donors, however, the risk and cost of inducing accommodation in the recipient would be reduced. An indirect assay of accommodation in the donor pig is needed for screening donors prior to procurement of the xenograft. The resistance of peripheral blood lymphocytes to cytolysis by antibody and complement was assessed in chimeric pigs and compared with control pigs. Peripheral blood lymphocytes (PBL) from chimeric pigs demonstrated a wide range of cytolysis (0 to 85%, median 13%) whereas PBL from control pigs were consistently lysed with these conditions (86 to 99%, median 96.5%, P < 0.0001). Accommodation or reduction in cytolysis did not correlate with the amount of chimerism. A longitudinal study demonstrated persistent accommodation of the PBL for as long as 15 weeks, when the donors averaged 68 kg in weight. Accommodation has been induced by low levels of antibodies interacting with the target tissue. An ELISA for sheep IgG was developed and the serum from newborn pigs assessed. Sheep IgG (up to 4.6 μg/ml) was detected in four of seven piglets with chimerism detectable by flow cytometry and in one of four piglets with minimal chimerism, detectable only by PCR. Lymphocyte accommodation was observed in all pigs with detectable sheep IgG. Of four pigs without accommodation, none had sheep IgG. Three pigs without detectable sheep IgG also had accommodation, suggesting that factors other than sheep IgG may induce accommodation. Acute vascular rejection was not observed in the heterotopic heart transplants from six donors with PBL accommodation. Only one incident of moderate diffuse cellular rejection (grade 3) was observed.

Original languageEnglish (US)
Pages (from-to)66-71
Number of pages6
JournalXenotransplantation
Volume10
Issue number1
DOIs
StatePublished - Jan 2003

Keywords

  • Accommodation
  • Acute vascular rejection
  • Fetal
  • Heart transplant
  • Immunoglobulin
  • Immunology
  • Intrauterine
  • Lymphocyte
  • Porcine
  • Rejection
  • Xenotransplantation

ASJC Scopus subject areas

  • Immunology
  • Transplantation

Fingerprint Dive into the research topics of 'Pre-transplant analysis of accommodation in donor pigs'. Together they form a unique fingerprint.

Cite this