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Memory T cells are significantly increased in rejected liver allografts of rhesus monkeys.

Authors
  • Kim, Hwajung1
  • Kim, Hyeyoung1
  • Lee, Sun-Kyung1
  • Jin, Xue-Li1
  • Kim, Tae Jin2
  • Park, Chanho2
  • Lee, Jae-Il3
  • Kim, Hyo-Sin1
  • Hong, Suk Kyun1
  • Yoon, Kyung Chul1
  • Ahn, Sung Woo1
  • Lee, Kyoung-Bun4
  • Yi, Nam-Joon1
  • Yang, Jaeseok1, 5
  • Lee, Kwang-Woong1
  • Hawthorne, Wayne J6
  • Suh, Kyung-Suk1
  • 1 Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea. , (North Korea)
  • 2 Division of Immunobiology, Sungkyunkwan University School of Medicine, Suwon, South Korea. , (North Korea)
  • 3 Department of Medicine, Seoul National University College of Medicine, Seoul, South Korea. , (North Korea)
  • 4 Department of Pathology, Seoul National University Hospital, Seoul, South Korea. , (North Korea)
  • 5 Transplantation Center, Seoul National University Hospital, Seoul, South Korea. , (North Korea)
  • 6 Department of Surgery, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia. , (Australia)
Type
Published Article
Journal
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
Publication Date
Feb 01, 2018
Volume
24
Issue
2
Pages
256–268
Identifiers
DOI: 10.1002/lt.24983
PMID: 29150986
Source
Medline
License
Unknown

Abstract

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 peripheral blood mononuclear cells (PBMCs) and secondary lymphoid organs along with livers of normal RMs and compared them with those of rejected LT recipients following withdrawal of immunosuppression. We undertook 5 allogeneic ABO compatible orthotopic LTs in monkeys using 5 normal donor monkey livers. We collected tissues including lymph nodes, spleens, blood, and recipient livers, and we performed flow cytometric analysis using isolated immune cells. We found that CD4 or CD8 naïve 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+ forkhead box P3+ T cells and CD8+ CD28- cells remained in high numbers in the liver, but not in the lymph nodes or PBMC. The comparison of CD4/8 T subpopulations in normal and rejected livers and the various tissues showed that naïve cells were dramatically decreased in the spleen, lymph node, and PBMCs of rejected LT monkeys, but rather, the memory CD4/8 T cells were increased in all tissues and PBMC. The normal liver has large numbers of CD4 regulatory T cells, 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 rejected liver allografts of RMs compared with those seen in normal RM tissues. Liver Transplantation 24 256-268 2018 AASLD.

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