1. Memory T cells are significantly increased in rejected liver allografts of rhesus monkeys
- Author
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Tae Jin Kim, Kyung-Suk Suh, Jaeseok Yang, Kyung Chul Yoon, Sun Kyung Lee, Hyo Sin Kim, Kyoung Bun Lee, Hyeyoung Kim, Hwajung Kim, Chan-Ho Park, Nam-Joon Yi, Xue Li Jin, Kwang-Woong Lee, Sung Woo Ahn, Wayne J. Hawthorne, Jae Il Lee, and Suk Kyun Hong
- Subjects
0301 basic medicine ,Graft Rejection ,Male ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Spleen ,030230 surgery ,Biology ,Liver transplantation ,03 medical and health sciences ,0302 clinical medicine ,T-Lymphocyte Subsets ,medicine ,Liver Immunology ,Animals ,Transplantation, Homologous ,Lymph node ,Transplantation ,Immunity, Cellular ,Hepatology ,CD28 ,Original Articles ,Allografts ,Macaca mulatta ,Immunity, Innate ,Liver Transplantation ,Disease Models, Animal ,030104 developmental biology ,Lymphatic system ,medicine.anatomical_structure ,Liver ,Immunology ,Surgery ,Original Article ,Lymph ,Lymph Nodes ,Immunologic Memory ,CD8 ,Allotransplantation - Abstract
Introduction: The Rhesus monkey (RM) is an excellent preclinical model in kidney, heart and islet transplantation that has provided the basis for new immunosuppressive protocols for clinical studies. However, there remain relatively few liver transplantation (LT) models in nonhuman primates. In this study, we analyzed the immune cell populations of PBMCs and secondary lymphoid organs along with livers of normal rhesus monkeys and compared them to those of rejecting liver transplanted recipient's following withdrawal of immunosuppression. Methods & Results: We undertook five allogeneic ABO compatible orthotopic LT in monkeys using five normal donor monkey livers. We collected tissues including lymph nodes, spleens, blood, recipient livers and performed flow cytometric analysis using isolated immune cells. We found that CD4 or CD8 naive T cells were normally seen at low levels and memory T cells were seen at high levels in the liver rather than lymphoid organs or PBMC. However, regulatory cells such as CD4+FoxP-3(+)T cells and CD8+CD28- cells remained in high numbers in the liver, but not in lymph node or PBMC. The comparison of CD4/8 T sub-populations in normal and rejected livers and the various tissues showed that naive cells were dramatically decreased in spleen, lymph node and PBMC of rejected liver transplanted monkeys, but rather memory CD4/8 T cells were increased in all tissues and PBMC. Conclusion: The normal liver has large numbers of CD4 Tregs, CD8+CD28- and myeloid-derived suppressor cells, which are known immunosuppressive cells occurring at much higher levels than those seen in lymph node or peripheral blood. Memory T cells are dramatically increased in rejecting liver allografts of rhesus monkeys compared to those seen in normal RM tissues. This article is protected by copyright. All rights reserved.
- Published
- 2017