T-CELL RESPONSES TO TUBERCULIN PURIFIED PROTEIN DERIVATIVE IN PRIMARYBILIARY-CIRRHOSIS - EVIDENCE FOR DEFECTIVE T-CELL FUNCTION

Background-Primary biliary cirrhosis (PBC) has an autoimmune aetiology , although little is known regarding the mechanisms of breakdown of se lf tolerance. One postulated mechanism of control of self tolerance is through interacting T cell subsets, a phenomenon explored in this stu dy. Aims-To characterise and compare T cell subset responses to an ant igen (tuberculin purified protein derivative derived from mycobacteria ) in PBC patients and controls. Cross reactive responses to mycobacter ia have recently been implicated in the aetiology of PBC. Subjects-58 PBC patients, 25 normal controls, and 34 chronic liver disease control s. Methods-Responses to antigen were measured in terms of primary T ce ll proliferation and cytokine secretion (by ELISA). Responding cells w ere phenotyped by FAGS analysis. Results-Similar CD4+ T cell prolifera tive responses were seen in PBC patients (mean (SD) stimulation index (SI) 22.6 (27.2), 42 of 58 (72.4%) positive response), normal controls (46.5 (88.0), 17 of 25 (68%) positive), and chronic liver disease con trols (24.8 (49.8), 27 of 34 (79.4%) positive)). Secretion of both int erferon gamma and IL10 was significantly lower in PBC patients than co ntrols (IFN gamma: PBC 822.7 (1100) pg/ml, controls 2929 (3402) pg/ml, p<0.05: IL10: PBC 11.1 (15.6) pg/ml, controls 34.7 (63.4) pg/ml, p<0. 05). Conclusions-In PBC unimpaired T cell proliferation is seen with r educed secretion of both Th-1 (interferon gamma) and Th-2 type (IL10) cytokines. These findings may result from differential subset response s and may help explain the defects of functional immunity seen in PBC.