High serum levels of CD8 antigen in primary biliary cirrhosis: a possible cause of suppressor cell dysfunction?

Abstract

Reduced suppressor cell number and function have been described in a number of autoimmune diseases and this may contribute to pathogenesis. Suppressor cell function depends upon the interaction of the CD8 antigen expressed on suppressor cells with other limbs of the immune system. Recently, soluble membrane antigens including CD8 have been identified in serum and it is possible that the loss of such antigens from viable cells could result in functional deficit. In order to examine whether the decreased suppressor cell function reported in autoimmune type of chronic liver disease is associated with soluble serum CD8 levels, sera from 23 patients with primary biliary cirrhosis (PBC), 12 with autoimmune chronic active hepatitis (AI-CAH) and 21 healthy controls were tested using a commercially available enzyme immunoassay. The proportion of cells expressing the CD8 antigen and the intensity of its display were also determined using an immunofluorescent technique and an ELISA, respectively, for 12 PBC and 10 healthy controls. The soluble serum CD8 levels were significantly higher in PBC (mean U/ml +/- s.d., 777 +/- 331), and AI-CAH (575 +/- 291) than controls (322 +/- 115) (P less than 0.001 and P = 0.004, respectively). While the intensity of CD8 antigen expression on suppressor/cytotoxic populations was not significantly different in PBC (347 +/- 125 per 10(4) cells) compared with controls (441 +/- 206), the mean proportion of CD8 positive cells was significantly less in PBC (14.1 +/- 6.8%) than controls (20 +/- 4.7%) (P less than 0.05). These data suggest that the apparent reduction in suppressor cell number found for patients with PBC and AI-CAH may be a consequence of the shedding or secretion of CD8 antigen from cell membrane of CD8 positive lymphocyte. It is also possible that the loss of this antigen is responsible for the reduced suppressor cell function seen in these conditions.