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. 2018 Feb 15;9(21):15552-15565.
doi: 10.18632/oncotarget.24514. eCollection 2018 Mar 20.

Description of organ-specific phenotype, and functional characteristics of tissue resident lymphocytes from liver transplantation donor and research on immune tolerance mechanism of liver

Yunpeng Shi  1 , Ping Zhang  1 , Guangyi Wang  1 , Xingkai Liu  1 , Xiaodong Sun  1 , Xin Zhang  2 , Haijun Li  3 , Jun Qi  1 , Lei Ding  1 , Ting Li  1 , Ruoyan Zhang  1 , Yuguo Chen  1 , Jianpeng Zhou  1 , Guoyue Lv  1 , Zhengkun Tu  1   3
Affiliations

Description of organ-specific phenotype, and functional characteristics of tissue resident lymphocytes from liver transplantation donor and research on immune tolerance mechanism of liver

Yunpeng Shi et al. Oncotarget. .

Abstract

Aim: Prior to transplantation, Donation after Cardiac Death (DCD) liver transplantation livers are perfused with preservation solution. Therefore, this provides an abundant source of human liver lymphocytes, as well as mesenteric lymph node and spleen for the study of lymphocyte subset diversity in the peripheral blood, lymph node, spleen and liver.

Methods: Lymphocyte subsets were isolated and purified from peripheral blood, lymph node, spleen and liver perfusion, the phenotypic and functional analysis of the tissue resident lymphocyte were performed by flow cytometry.

Results: In a direct comparison between blood, liver, lymph node and spleen cells from liver transplantation donors, the abundance of natural killer (NK) cells, CD3+CD56+NKT (NT) cells and CD8+ T cells in intrahapatic lymphocytes (IHL) did not match what was present in peripheral blood and other peripheral lymphoid organs. The activation state of peripheral blood-derived lymphocytes was significantly different from lymph node-, spleen- and liver-derived cells. Intriguingly, NK cells, CD4+ T cells, and CD8+ T cells from liver perfusion display more suppressive characteristics, that is, express and produce more anti-inflammatory cytokine interleukin (IL)-10, less inflammatory cytokine interferon (INF)-γ.

Conclusion: Our findings imply that different tissues entail resident lymphocyte subsets with a distinct phenotype and function considering the organ is well vascularized, particularly in liver. It is better to understand the mechanism of liver immune tolerance.

Keywords: intrahepatic lymphocytes; liver immune tolerance; liver transplantation.

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Conflict of interest statement

CONFLICTS OF INTEREST None.

Figures

Figure 1
Figure 1. The comparison of intrahepatic lymphocytes subsets isolated from liver perfusion and liver tissue
A complete DCD transplantation donor liver was released for research by the organ procurement organization after a transplant operation was aborted, and there was insufficient time to locate an alternative recipient. The availability of this liver allowed us to make a back-to-back comparison of different techniques of IHL isolation. Intrahepatic lymphocytes subsets isolated from liver perfusion and liver tissue before perfusion in the donor by traditional mechanical homogenization and enzymatic digestion methods.
Figure 2
Figure 2. The frequency comparison of lymphocyte subsets derived from peripheral blood, lymph node, spleen, and liver perfusion of liver donors
Mononuclear cells were isolated from peripheral blood, lymph node, spleen, and liver perfusion of 21 transplantation donors. The frequency of lymphocyte subsets were performed by flow cytometry. (A) Representative FACS data from a single donor. (B) Statistic analysis from 21 transplantation donors (n = 21, *P < 0.05).
Figure 3
Figure 3. Activation markers on lymphocyte subsets among the blood cells (PBMC), lymph node cells, spleen cells and IHL from transplantation donors
Mononuclear cells were isolated from peripheral blood, lymph node, spleen, and liver perfusion of 21 liver donors. The phenotypic analysis of lymphocytes subsets was also performed by gating on CD3-CD56+ NK cells, CD3+CD56+ NT cells, CD3+CD4+ T, and CD3+CD8+ T cells (A, C, E, G) Representative FACS data of NK cells, CD56+ T cells, CD4+, CD8+ T cells from a single donorin the peripheral blood, lymph node, spleen and liver perfusion. (B, D, F, H) Phenotypic analysis of NK cells, NT cells, CD4+, CD8+ T cells from 21 liver donors (n = 21, *P < 0.05, #P < 0.01).
Figure 4
Figure 4. Functional analysis of the cytokines of INF-γ and IL-10 secretion from the lymphocyte of the peripheral blood and donor liver perfusion
Our phenotypic analysis was performed by gating on CD3–CD56+ NK cells, CD3+CD4+ T, and CD3+CD8+ T cells. Representative IFN-γ and IL-10 expression data of NK cells, CD4+, CD8+ T cells from a single donor in the peripheral blood and liver perfusion were analyzed in A. Functional analysis of inflammatory and anti-inflammatory cytokine expression of NK cells, CD4+, CD8+ T cells from 21 liver donors (n = 21, *P < 0.05, #P < 0.01) was performed in B.
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References

    1. Blum KS, Pabst R. Lymphocyte numbers and subsets in the human blood. Do they mirror the situation in all organs? Immunol Lett. 2007;108:45–51. https://doi.org/10.1016/j.imlet.2006.10.009. - DOI - PubMed
    1. Olszewski WL. The lymphatic system in body homeostasis: physiological conditions. Lymphat Res Biol. 2003;1:11–21. https://doi.org/10.1089/15396850360495655. - DOI - PubMed
    1. Williams MB, Butcher EC. Homing of naive and memory T lymphocyte subsets to Peyer’s patches, lymph nodes, and spleen. J Immunol. 1997;159:1746–52. - PubMed
    1. Fulgenzi A, Casati R, Colombo FR, Gasparini M, Ferrero E, Bondanza A, Gerundini P, Ferrero ME. Distribution of 99mTc-labeled lymphocytes in control and inflamed rats. Nucl Med Biol. 2004;31:631–38. https://doi.org/10.1016/j.nucmedbio.2004.01.004. - DOI - PubMed
    1. Westermann J, Söllner S, Ehlers EM, Nohroudi K, Blessenohl M, Kalies K. Analyzing the migration of labeled T cells in vivo: an essential approach with challenging features. Lab Invest. 2003;83:459–69. https://doi.org/10.1097/01.LAB.0000062852.80567.90. - DOI - PubMed