Abstract
AimPrior 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.MethodsLymphocyte 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.ResultsIn 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.ConclusionOur 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.
Highlights
Lymphocytes migration from the blood across the non-lymphoid and lymphoid tissues through lymphatic system secured the parenchymal cells, tissues and organs is a prerequisite for immune surveillance [1, 2]
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
Summary
Lymphocytes migration from the blood across the non-lymphoid and lymphoid tissues through lymphatic system secured the parenchymal cells, tissues and organs is a prerequisite for immune surveillance [1, 2] Depending on their distinct functions, the resident lymphocytes in different organs and the migration pathways of lymphocytes in the lymphoid system and peripheral nonlymphoid tissue can vary [3,4,5,6]. Bone marrow hematopoietic stem cells can differentiate into NKPs, and early lymphoid precursors (ELPs) can differentiate into NKPs. In recent years, studies have confirmed the presence of NKPs in the liver, lymph nodes, spleen, indicating that all these tissues and organs can be the site of NK cell development and differentiation. Studies in mice have revealed an important role for tissue resident memory CD4+ and CD8+ T cells in protective immunity to site-specific pathogens [14,15], and these tissue-retained memory populations do not recirculate [16,17,18]
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