PHENOTYPIC AND FUNCTIONAL-CHARACTERISTICS OF LYMPHOCYTES ISOLATED FROM LIVER-BIOPSY SPECIMENS FROM PATIENTS WITH ACTIVE LIVER-DISEASE

Liver-derived lymphocytes were isolated from 73 liver biopsy specimens obtained from patients with chronic active liver disease and from six samples of normal liver. Mean absolute numbers (+/- S.E.M) of liver-derived lymphocytes recovered from needle biopsy specimens by mild enzymatic digestion of the liver tissue varied from 0.7 +/- 0.3 x 10(3)/mm3 in allografts being rejected to 8.9 +/- 0.9 x 10(3)/mm3 in chronic non-A, non-B hepatitis. By two-color flow cytometry, T lymphocytes (CD3+) were the major liver-derived lymphocyte population in all biopsy specimens. The mean CD4/CD8 ratio (0.6 +/- 0.2) was similar for liver-derived lymphocytes obtained from samples of normal or diseased liver. However, activated (human leukocyte antigen DR+) T cells were significantly (p < 0.05) increased in liver-derived lymphocytes obtained from liver disease specimens than they were in samples from normal livers. Natural killer cells were less numerous than T cells in specimens obtained from diseased livers, with the mean natural killer/T cell ratio ranging from a low of 0.1 in allograft rejection to a high of 0.8 +/- 0.3 in primary sclerosing cholangitis. Liver-derived lymphocytes isolated from diseased liver contained significantly fewer (p < 0.05) CD3-CD56+ or CD56+CD16-natural killer cells than did those obtained from normal liver samples. Natural killer activity was consistently detectable in liver-derived lymphocytes obtained from specimens of normal or diseased livers. Moreover, natural killer activity in the liver did not differ significantly from that in either normal or patient peripheral blood. Spontaneous cytotoxic activity against natural killer-resistant targets, Daudi cells, was detectable but low in liver-derived lymphocytes obtained from specimens of both normal and diseased livers. In liver-derived lymphocytes obtained from livers with chronic active liver disease, the proportion of natural killer cells was reduced; T lymphocytes were more prominent and displayed human leukocyte antigen DR antigens more frequently than in end-stage liver disease.