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Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model
When hyperacute rejection is avoided by deletion of Gal expression in the pig, delayed xenograft rejection (DXR) becomes a major immunologic barrier to successful xenotransplantation. This study was to investigate the potential antigens involved in DXR. We isolated primary renal microvascular endoth...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577312/ https://www.ncbi.nlm.nih.gov/pubmed/28855711 http://dx.doi.org/10.1038/s41598-017-10805-0 |
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author | Zhang, Junfang Xie, Chongwei Lu, Ying Zhou, Ming Qu, Zepeng Yao, Da Qiu, Chuanghua Xu, Jia Pan, Dengke Dai, Yifan Hara, Hidetaka Cooper, David K. C. Ma, Shanshan Li, Mingtao Cai, Zhiming Mou, Lisha |
author_facet | Zhang, Junfang Xie, Chongwei Lu, Ying Zhou, Ming Qu, Zepeng Yao, Da Qiu, Chuanghua Xu, Jia Pan, Dengke Dai, Yifan Hara, Hidetaka Cooper, David K. C. Ma, Shanshan Li, Mingtao Cai, Zhiming Mou, Lisha |
author_sort | Zhang, Junfang |
collection | PubMed |
description | When hyperacute rejection is avoided by deletion of Gal expression in the pig, delayed xenograft rejection (DXR) becomes a major immunologic barrier to successful xenotransplantation. This study was to investigate the potential antigens involved in DXR. We isolated primary renal microvascular endothelial cells (RMEC) and aortic endothelial cells (AEC) from a GGTA1/CMAH double-knockout (DKO) pig (and a GGTA1-KO pig) and immunized cynomolgus monkeys with both of these cells. After sensitization, monkey serum antibody binding and cytotoxicity to RMEC was significantly higher than to AEC(p < 0.05), suggesting that RMEC are more immunogenic than AEC. Transcriptome sequencing of GGTA1/CMAH DKO pigs indicated that the expression of 1,500 genes was higher in RMEC than in AEC, while expression of 896 genes was lower. Next, we selected 101 candidate genes expressed only in pig RMEC, but not in pig AEC or in monkey or human RMEC. When these genes were knocked out individually in GGTA1/CMAH DKO RMEC, 32 genes were associated with reduced antibody binding, indicating that these genes might be primary immunologic targets involved in DXR. These genes may be important candidates for deletion in producing pigs against which there is a reduced primate immune response in pig kidney xenograft. |
format | Online Article Text |
id | pubmed-5577312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55773122017-09-06 Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model Zhang, Junfang Xie, Chongwei Lu, Ying Zhou, Ming Qu, Zepeng Yao, Da Qiu, Chuanghua Xu, Jia Pan, Dengke Dai, Yifan Hara, Hidetaka Cooper, David K. C. Ma, Shanshan Li, Mingtao Cai, Zhiming Mou, Lisha Sci Rep Article When hyperacute rejection is avoided by deletion of Gal expression in the pig, delayed xenograft rejection (DXR) becomes a major immunologic barrier to successful xenotransplantation. This study was to investigate the potential antigens involved in DXR. We isolated primary renal microvascular endothelial cells (RMEC) and aortic endothelial cells (AEC) from a GGTA1/CMAH double-knockout (DKO) pig (and a GGTA1-KO pig) and immunized cynomolgus monkeys with both of these cells. After sensitization, monkey serum antibody binding and cytotoxicity to RMEC was significantly higher than to AEC(p < 0.05), suggesting that RMEC are more immunogenic than AEC. Transcriptome sequencing of GGTA1/CMAH DKO pigs indicated that the expression of 1,500 genes was higher in RMEC than in AEC, while expression of 896 genes was lower. Next, we selected 101 candidate genes expressed only in pig RMEC, but not in pig AEC or in monkey or human RMEC. When these genes were knocked out individually in GGTA1/CMAH DKO RMEC, 32 genes were associated with reduced antibody binding, indicating that these genes might be primary immunologic targets involved in DXR. These genes may be important candidates for deletion in producing pigs against which there is a reduced primate immune response in pig kidney xenograft. Nature Publishing Group UK 2017-08-30 /pmc/articles/PMC5577312/ /pubmed/28855711 http://dx.doi.org/10.1038/s41598-017-10805-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhang, Junfang Xie, Chongwei Lu, Ying Zhou, Ming Qu, Zepeng Yao, Da Qiu, Chuanghua Xu, Jia Pan, Dengke Dai, Yifan Hara, Hidetaka Cooper, David K. C. Ma, Shanshan Li, Mingtao Cai, Zhiming Mou, Lisha Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model |
title | Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model |
title_full | Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model |
title_fullStr | Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model |
title_full_unstemmed | Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model |
title_short | Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model |
title_sort | potential antigens involved in delayed xenograft rejection in a ggta1/cmah dko pig-to-monkey model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577312/ https://www.ncbi.nlm.nih.gov/pubmed/28855711 http://dx.doi.org/10.1038/s41598-017-10805-0 |
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