Potential role of resident intrahepatic lymphocytes in adoptive transfer of immunity to hepatitis B virus through liver transplantation

Abstract

Background & Aims: Both murine and human studies have demonstrated the adoptive transfer of hepatitis B virus (HBV)-specific immunity through liver transplantation, which may be attributed to the presence of a significant number of immunocompetent cells in the liver grafts from donors with HBV immunity. In this study, we characterized the resident lymphocytes in human liver grafts, identified the HBV-specific lymphocytes in liver grafts from HBV immune donors, and evaluated the potential role of the intrahepatic lymphocytes in the adoptive transfer of HBV immunity through liver transplantation. Methods: The number, location, and phenotype of resident lymphocytes in human liver grafts were determined by immunohistochemical staining and flow cytometry. The frequency of HBV-specific T cells and B cells was quantified directly by enzyme-linked immunospot (ELISPOT) assay. The serum antibody against hepatitis B surface antigen (anti-HBs) was tested by enzyme immunoassay. Results: The resident lymphocytes were predominantly located in the portal tracts and also scattered throughout the parenchyma of normal liver tissue. Natural Killer (NK) cells (CD 56 ) constituted 27.69.1% of total resident lymphocytes in liver grafts. The majority of intrahepatic CD3 T cells expressed CD8 (67.314.1%), while a smaller proportion expressed CD4 (23.39.7%). NK-T cells bearing both CD3 and CD56 constituted 29.718.1% of intrahepatic CD3 T cells. B cells (CD20 ) accounted for 6.33.8% of the total resident lymphocytes in liver grafts. A significant number of IFN- -secreting T cells specific for HBV antigens were observed in 72.4% (21/29) of liver grafts from donors who are immune to HBV. The anti-HBs-secreting B cells were also detected in 27.6% (8/29) of liver grafts by ELISPOT assay. Spontaneous development of seroconversion to anti-HBs status has been observed in 40.6% (13/32) of patients who underwent liver transplantation for chronic hepatitis B, which was significantly related with the serum anti-HBs level of liver donors and HBsAg-specific T cell number in liver grafts before implantation. Conclusions: Normal liver graft contains a significant number of resident lymphocytes with distinct phenotype. The presence of HBV-specific immunocompetent cells in liver grafts from HBV immune donors may account for the donor-derived immunity to HBV in liver recipients.