Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response

James R. Butler, Zheng Yu Wang, Gregory R. Martens, Joseph M. Ladowski, Ping Li, Matthew Tector, A. Joseph Tector

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells.

Original languageEnglish (US)
Pages (from-to)47-51
Number of pages5
JournalTransplant Immunology
Volume35
DOIs
StatePublished - Mar 1 2016

Fingerprint

Heterologous Transplantation
Polysaccharides
Swine
T-Lymphocytes
Clustered Regularly Interspaced Short Palindromic Repeats
Mixed Lymphocyte Culture Test
Thomsen-Friedenreich antibodies
Heterografts
Immunosuppression
Allografts
Blood Cells
Spleen
Lymphocytes
Antibodies
Genes

Keywords

  • Cellular responses
  • Glycan
  • Sialic acid
  • T cell
  • Xenotransplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation

Cite this

Butler, J. R., Wang, Z. Y., Martens, G. R., Ladowski, J. M., Li, P., Tector, M., & Tector, A. J. (2016). Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response. Transplant Immunology, 35, 47-51. https://doi.org/10.1016/j.trim.2016.02.001

Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response. / Butler, James R.; Wang, Zheng Yu; Martens, Gregory R.; Ladowski, Joseph M.; Li, Ping; Tector, Matthew; Tector, A. Joseph.

In: Transplant Immunology, Vol. 35, 01.03.2016, p. 47-51.

Research output: Contribution to journalArticle

Butler, James R. ; Wang, Zheng Yu ; Martens, Gregory R. ; Ladowski, Joseph M. ; Li, Ping ; Tector, Matthew ; Tector, A. Joseph. / Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response. In: Transplant Immunology. 2016 ; Vol. 35. pp. 47-51.
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