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Memory T cells are significantly increased in rejected liver allografts of rhesus monkeys
Author(s) -
Kim Hwajung,
Kim Hyeyoung,
Lee SunKyung,
Jin XueLi,
Kim Tae Jin,
Park Chanho,
Lee JaeIl,
Kim HyoSin,
Hong Suk Kyun,
Yoon Kyung Chul,
Ahn Sung Woo,
Lee KyoungBun,
Yi NamJoon,
Yang Jaeseok,
Lee KwangWoong,
Hawthorne Wayne J.,
Suh KyungSuk
Publication year - 2018
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.24983
Subject(s) - cd8 , peripheral blood mononuclear cell , cd28 , immune system , spleen , medicine , immunosuppression , immunology , liver transplantation , lymph , lymph node , t cell , cytotoxic t cell , transplantation , lymphatic system , biology , pathology , biochemistry , in vitro
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.