CD45ROhighCD57+CD8high T cells in primary biliary cirrhosis (101.4)

Abstract

Abstract Primary biliary cirrhosis (PBC) is a female predominant organ specific autoimmune disease with specific destruction of intrahepatic small biliary epithelial cells (BECs). Patients develop a multilineage response to the E2 component of pyruvate dehydrogenase (PDC-E2) involving autoantibody as well as autoreactive CD4 and CD8 T cell responses. Recent data from murine PBC models have suggested that liver-infiltrating CD8 T cells play a critical role in biliary destruction in PBC. Many studies suggest the augmented cytotoxicity of CD57+CD8 T lymphocytes. Therefore, we have studied the frequencies and phenotypic characterization of CD8highCD57+ T lymphocyte components in both patients with PBC and age matched controls. Our data indicate that CD45ROhighCD57+CD8high T lymphocytes from PBC patients, but not controls, have significant phenotypic alterations, including increased expression α4β7high and reduced expression of annexin V after TCR stimulation. Our data also indicate that patient CD45ROhighCD57+CD8high T cells express higher granzyme A, B, perforin, CCR5 and α4β7, reduced expression of CCR7 than other CD8high T cells. Furthermore, IFN-γ and IL-5 productions by CD57+CD8high T lymphocytes upon in vitro TCR stimulation are increased in PBC patients. In conclusion, our data demonstrate that CD45ROhighCD57+CD8high T cells are a subset of cytotoxic memory cells which play a critical role in the chronic and progressive destruction of BECs in PBC.