Abnormal natural killer cytotoxicity in primary biliary cirrhosis: Evidence for a functional deficiency of cytolytic effector cells

Abstract

The in vitro cytotoxic activity of peripheral blood lymphocytes from patients with primary biliary cirrhosis was investigated to determine the mechanism of deficient spontaneous cell-mediated cytotoxicity in this disease. Using 51Cr-labeled Chang or K562 target cells, it was found that patients' lymphocytes mediated less natural killer cytotoxicity than lymphocytes from normal controls. Antibody-dependent cytotoxicity was normal in primary biliary cirrhosis. The natural killer activity of normal lymphocytes was inhibited neither by serum nor by lymphocytes from patients with primary biliary cirrhosis. The percentage of lymphocytes from patients that bound to target cells was normal. Furthermore, the percentages of lymphocytes that reacted with the monoclonal antibodies anti-Leu-7 and anti-Leu-11 were normal in patients. The percentage of lymphocytes that reacted with both anti-Leu-2 and anti-Leu-7, a subpopulation of cells that has low natural killer activity, was also normal in primary biliary cirrhosis. Interferon and interleukin-2 both augmented cytotoxic function of lymphocytes from primary biliary cirrhosis patients, however, the levels of cytotoxicity induced by these agents were less than corresponding levels exhibited by normal lymphocytes when similarly stimulated. These findings indicate that patients with primary biliary cirrhosis have diminished natural killer activity due to a functional defect of cytolytic effector cells.