Skip to main content
. 2020 Sep 2;11:2155. doi: 10.3389/fimmu.2020.02155

FIGURE 1.

FIGURE 1

(A) Acute TCMR 6 days post liver transplant. This high-power image (hematoxylin & eosin (H&E), ×600) of a portal tract shows infiltration of a large number of inflammatory cells. Typical examples of a lymphocyte (square), neutrophil (triangle), eosinophil (circle) and two macrophages (hexagon) are highlighted, demonstrating the contribution of cells from both the innate and adaptive immune systems. The majority of the lymphocytes will be T-cells, capable of mediating cell damage through direct cytotoxicity and the release of pro-inflammatory cytokines. There is clustering around the bile duct (B) and portal vein (PV, inset, with damage to endothelium seen at 4 o’clock). Neutrophils and macrophages migrate to the liver in response to pro-inflammatory cytokines, enhanced by Th1 and Th17 responses. Eosinophils are also present in early rejection infiltrates and are more typically associated with a Th2 response. Treatment with high dose pulsed methylprednisolone was able to suppress the rejection episode in this patient and tolerance has since been maintained using a standard immunosuppressive regimen. (B) Immune tolerance 8 days post liver transplant. In contrast to Figure 2A, a portal tract from this biopsy (H&E, ×600) contains only a small number of lymphocytes, macrophages and neutrophils with no evidence of damage to biliary epithelium (B) or portal vein endothelium (PV). Tolerance to the liver allograft is promoted by multiple factors including the relatively low levels of MHC class II expression on hepatic-resident cells, a tendency toward tolerogenic antigen presentation by the dendritic cells, macrophages, stellate cells and epithelial cells resident in the liver, the dominance of a regulatory T-cell infiltrate and the action of donor-derived NK cells on the recipient immune system. Indeed, a biliary complication of surgery was found to be the reason for liver dysfunction in this patient, and tolerance was maintained on follow-up by means of a standard immunosuppressive regimen without the need for additional therapy.