Lymphocyte suppressor cell activity in acute and chronic liver disease.

We investigated lymphocyte suppressor cell activity in 53 patients with acute and chronic liver diseases. Suppressor cells were generated by preincubation of peripheral blood mononuclear cells (PBM) with concanavalin A (Con A) for 48 hr. Suppressor cell activity was evaluated by inhibition of Con A-stimulated blast transformation and by inhibition of pokeweed mitogen-induced immunoglobulin (Ig) synthesis of fresh allogeneic normal PBM in the second-set cultures. Of 29 patients with chronic active liver diseases (CALD), defective suppressor cell activities were observed in eight cases (28%) for Ig synthesis and 16 cases (55%) for blast transformation study. The suppressor cell activities were decreased in two (22%) of nine cases with chronic persistent hepatitis and one (17%) of six cases with inactive cirrhosis for both Ig synthesis and blast transformation. In contrast, suppressor activities were inducible in all nine patients with acute viral hepatitis. The histocompatibility antigen DR4 was significantly increased in CALD patients, but there was no correlation between this antigen and suppressor cell activity. These findings suggest that altered lymphocyte suppressor cells in patients with CALD may contribute to the continuing liver cell injury in this disease.

Immunoregulatory T-cell function in acute and chronic liver disease.

The suppressor function of T cells separated from the peripheral blood lymphocytes of patients with acute or chronic liver disease was evaluated by using, as an indicator system, pokeweed mitogen-induced immunoglobulin synthesis in vitro. Suppressor activity of T cells was enhanced during the recovery phase in 13 or 17 patients who have recovered from acute viral hepatitis. When such T cells were irradiated before coculture, the suppressor function was selectively eliminated, but the helper T-cell function remained unchanged. In serial studies, normalization of the excess suppressor function of T cells was observed when the liver function of an acute viral hepatitis patient returned to the normal range. Except for chronic active liver disease, in which the suppressor activity of T cells was substantially reduced in 50% of the patients studied. the studies indicated normal T-cell functions, both suppressor and helper, in other liver diseases such as chronic persistent hepatitis, inactive cirrhosis, and fatty liver disease. These data sugest that the host immunoregulatory mechanism might be important in recovering from acute viral hepatitis and in perpetuating hepatocyte injury in chronic active liver disease.

Occurrence and significance of antibody to liver-specific membrane lipoprotein by double-antibody immunoprecipitation method in sera of patients with acute and chronic liver diseases.

A double-antibody immunoprecipitation method was developed for detecting antibody to liver-specific membrane lipoprotein (anti-LSP) in sera of patients with various liver diseases and primary nonhepatic autoimmune diseases. Liver-specific membrane lipoprotein prepared from normal rat livers was labeled with 125I (chloramine-T) and monospecific antibody raised in rabbits. Cross-reactivity and absorption studies demonstrated that the assay used was highly specific. The frequency and titer of anti-LSP were similar for HBsAg-positive and -negative patients with both acute and chronic liver diseases. Patients with chronic active hepatitis had the highest frequenzy (25 of 44 cases, 57%) when compared with those with chronic persistent hepatitis (5 of 23 cases, 22%) and nonalcoholic cirrhosis (8 of 21 cases, 38%). Of the anti-LSP positive cases, the mean titer in patients with chronic active hepatitis tended to be the highest. In patients recovered from acute viral hepatitis, anti-LSP was transiently positive (7 of 20 cases, 35%) in the acute phase. In those who progressed to chronic hepatitis, a late rise as well as an early rise occurred in 6 of 10 patients before the diagnosis was made. Two of 6 patients with primary biliary cirrhosis had anti-LSP, but none of 41 patients with other nonviral liver diseases and none of 60 patients with primary nonhepatic autoimmune diseases. These data indicate that an autoimmune reaction directed against LSP can be initiated during the acute phase of viral hepatitis and it may persist in chronic hepatitis in both HBsAg-positive and -negative cases.