Chronic active hepatitis B. Interferon-activated natural killer-like cells against a hepatoma cell line transfected with the hepatitis B virus nucleic acid.
In a rapid 51Cr release assay, peripheral blood mononuclear cells from 12 healthy donors did not lyse the hepatitis B virus deoxyribonucleic-acid-transfected human hepatoma cell line 2.2.15, but under the same experimental conditions they did lyse K562 cells. Peripheral blood mononuclear cells from 10 out of 16 patients with chronic active hepatitis B exhibited cytotoxic activity against 2.2.15 cells in the presence of a relatively reduced natural killer cell activity to the K562 cell target. Enhancement of the cytotoxic activity to 2.2.15 cells was statistically significant in the group of patients being treated with leukocyte alpha-interferon. The activity was not influenced by the degree of human leukocyte antigen type matching between effector and target, and was enhanced by depletion of T-cells and by in vitro interferon treatment. These results therefore support the concept of a natural killer-like cell activated by clinical administration of interferon in chronic active hepatitis B patients. This cell effector was lytic for the virus B negative HEP-G2 cells also. However, T-cells purified from a few patients failed to lyse the HEP-G2 while lysing the 2.2.15 target, thus indicating that a preferential recognition of the virus-infected target may be exerted by certain T-lymphocyte subsets. The use of the human leukocyte antigen type defined, highly differentiated, hepatitis B virus releasing 2.2.15 cell line as target for fresh lymphocytes in this cytolytic assay did not disclose cytolytic T-cells in an obvious way. Further manipulation of this system perhaps using T-cell clones may be the next step to exploit the investigative possibilities offered by the availability of the 2.2.15 cell target.
Actis
G C
GC
Divisione di Gastroenterologia, Ospedale Molinette, Torino, Italy.
Ponzetto
A
A
D'Urso
N
N
Saracco
G
G
Crepaldi
T
T
Bellone
G
G
Catucci
L M
LM
Zarcone
D
D
Verme
G
G
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D006509:Hepatitis B / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics*; D006521:Hepatitis, Chronic / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D004279:DNA, Viral; D007370:Interferon Type I