T cell responses to tuberculin purified protein derivative in primary biliary 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 self tolerance. One postulated mechanism of control of self tolerance is through interacting T cell subsets, a phenomenon explored in this study. AIMS: To characterise and compare T cell subset responses to an antigen (tuberculin purified protein derivative derived from mycobacteria) in PBC patients and controls. Cross reactive responses to mycobacteria have recently been implicated in the aetiology of PBC. SUBJECTS: 58 PBC patients, 25 normal controls, and 34 chronic liver disease controls. METHODS: Responses to antigen were measured in terms of primary T cell proliferation and cytokine secretion (by ELISA). Responding cells were phenotyped by FACS analysis. RESULTS: Similar CD4+ T cell proliferative 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 controls (24.8 (49.8), 27 of 34 (79.4%) positive)). Secretion of both interferon gamma and IL10 was significantly lower in PBC patients than controls (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 reduced secretion of both Th-1 (interferon gamma) and Th-2 type (IL10) cytokines. These findings may result from differential subset responses and may help explain the defects of functional immunity seen in PBC.