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Cultured with a liver-derived lipoprotein complex, T lymphocytes from 42 of 45 patients with autoimmune chronic active hepatitis generated migration inhibitory factor compared with 16 of 33 patients with primary biliary cirrhosis. Unlike T lymphocytes from patients with primary biliary cirrhosis, the T-cell reactivity of patients with chronic active hepatitis was always suppressed by T cells from normal subjects and, with two exceptions, by T cells from patients with primary biliary cirrhosis, even when these latter cells exhibited sensitization to this same antigen complex. Using a component of the whole complex, the asialoglycoprotein receptor as antigen, migration inhibitory factor was invariably released by T cells from patients with autoimmune chronic active hepatitis, but from only 2 of 8 patients with primary biliary cirrhosis sensitized to the whole complex. Thus, in autoimmune chronic active hepatitis, but not in primary biliary cirrhosis, the asialoglycoprotein receptor is invariably a target for cellular immune reactions and is associated with a suppressor T-cell defect for hepatocyte antigens.

An indirect migration inhibition assay has been used to show that lymphocytes from 26 of 29 patients with autoimmune chronic active hepatitis (CAH) generated T lymphocyte migration inhibitory factors (T-LIF) in the presence of liver specific protein (LSP), compared with only 1 of 21 patients with HBsAg-positive chronic liver disease and none of 19 controls. Generation of T-LIF activity in response to LSP was not observed in any of 5 patients with autoimmune thyroid disease although their T lymphocytes did generate T-LIF activity in the presence of thyroid membrane antigens. T lymphocytes from 1 patient with autoimmune liver and thyroid disease generated T-LIF activity in the presence of both LSP and thyroid membrane antigens. The generation of T-LIF activity by T cells from autoimmune CAH patients was suppressed when these cells were co-cultured in a 9:1 ratio with T cells from normal subjects and patients with HBsAg-positive chronic liver disease, but was unaffected if co-cultured with T cells from other patients with autoimmune CAH. T cells from patients with autoimmune CAH did, however, suppress the generation of T-LIF activity by T lymphocytes from patients with autoimmune thyroid disease when these cells were cultured with thyroid membrane antigens. After pretreatment with cimetidine or mitomycin-C for 30 min, T cells from normal subjects lost their ability to inhibit the generation of T-LIF activity to T lymphocytes from autoimmune CAH patients. These results are consistent with the hypothesis that there exists a defect in the specific suppressor T cell population controlling the immune response to LSP in autoimmune CAH which is unaffected by disease activity and treatment and which may be of fundamental importance in the pathogenesis of the disease.

Analysis of the behaviour and chronological development of B virus markers (including those most recently identified) in acute and chronic hepatitis gives rise to a diagnostic hypothesis about their presence and association. The prognostic and therapeutic significance of the markers is also emphasised with particular reference to fulminating and chronic active HBSAg and D positive hepatitis and the early diagnosis of liver cell carcinoma.