T-lymphocyte subsets in liver tissues of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls

Abstract

T lymphocytes infiltrating hepatic tissues were typed and enumerated in liver biopsies of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls using monoclonal antibodies and the avidin-biotin-immunoperoxidase technique. The peripheral blood mononuclear cells were studied also by flow cytometry. In PBC, T lymphocytes were decreased (P less than 0.001) in the blood [absolute number was 426 +/- 200 (SE) vs 1351 +/- 416 in 15 controls], as was the helper/suppressor (T4/T8) ratio (1.0 +/- 0.1 vs normal 2.3 +/- 0.3). T lymphocytes were the most numerous mononuclear cells infiltrating portal areas of PBC livers: 749 +/- 93/5 high-power fields (HPF) in PBC vs 98 +/- 15/5 HPF (P less than 0.01) in controls. The T4/T8 ratios varied from 0.9 to 2.3 (mean, 1.8 +/- 0.1) in the portal triads (normal mean, 1.6 +/- 0.1), with the T4+ cells accounting for more than 75% of infiltrating T cells. In contrast, the mean T4/T8 ratio in portal triads of PSC was reduced (1.0 +/- 0.3) due to a significant increase (P less than 0.001) in the number of T8+ cells. The T cells around and in the walls of bile ducts in PBC were mostly T8+, and the T4/T8 ratio was 0.8 +/- 0.2. No T8+ cells were seen in this location in PSC and normal livers. Few mononuclear cells were present in hepatic lobules. Subtyping of T lymphocytes in liver tissues of patients with PBC and PSC may be helpful in the differential pathologic diagnosis. In patients with advanced PBC, a decrease in T4+ cells in the blood appeared to be accompanied by their accumulation in the portal triads. In contrast, T8+ cells accumulated preferentially around bile ducts.

Fig. 1

The numbers of T lymphocytes, T4+ cells, and T8+ cells in portal tracts of livers in patients with primary biliary cirrhosis (●) and sclerosing cholangitis (▲) and in normal livers (○). The horizontal bars indicate means. The vertical lines denote ±1 SD.

Fig. 2

T lymphocytes in liver tissues of patients with primary biliary cirrhosis. T cells were seen scattered in the septa and infiltrating parenchyma in the areas adjacent to septa. Limiting plates were frequently especially strongly infiltrated. Focal accumulations of T cells could be found in the septa (a) or in liver parenchyma. Most of the T lymphocytes in the portal areas were T4+ (b). The minority bad a T8 phenotype (c). The ABC techniques. ×400.

Fig. 2

T lymphocytes in liver tissues of patients with primary biliary cirrhosis. T cells were seen scattered in the septa and infiltrating parenchyma in the areas adjacent to septa. Limiting plates were frequently especially strongly infiltrated. Focal accumulations of T cells could be found in the septa (a) or in liver parenchyma. Most of the T lymphocytes in the portal areas were T4+ (b). The minority bad a T8 phenotype (c). The ABC techniques. ×400.

Fig. 3

T lymphocytes around the bile ducts in the liver biopsy of a patient with primary biliary cirrhosis (a). The T8+ lymphocytes (b) are more numerous in this area than T4+ lymphocytes (c); see arrows. ×640.

Fig. 3

T lymphocytes around the bile ducts in the liver biopsy of a patient with primary biliary cirrhosis (a). The T8+ lymphocytes (b) are more numerous in this area than T4+ lymphocytes (c); see arrows. ×640.