Masumi Kanai

Flow cytometric and functional analysis of mononuclear cells infiltrating the liver in experimental autoimmune hepatitis

Experimental autoimmune hepatitis was produced by immunizing Wistar rats with syngeneic liver proteins. Mononuclear cells infiltrating the liver tissue were identified by immunohistochemical techniques using monoclonal antibodies specific for subpopulations of rat lymphocytes. The strong infiltration of CD8+ cytotoxic T lymphocytes (CTL) were found in the portal areas. Subpopulations of mononuclear cells infiltrating the liver, spleen cells and peripheral blood lymphocytes were identified by flow cytometry. Flow cytometric analysis revealed the presence of CD5‐ and CD8+ lymphocytes in the liver tissues. Mononuclear cells infiltrating the liver were isolated from Wistar rats having autoimmune hepatitis to determine whether those exhibit cytotoxicity against syngeneic hepatocytes; they exhibited cytotoxicity against isolated syngeneic hepatocytes, but failed to lyse K562 cells, syngeneic concanavalin A‐activated splenocytes and allogeneic hepatocytes. Depietion of CD8+ T cells significantly reduced the cytotoxic ability of mononuclear cells infiltrating into the liver against syngeneic hepatocytes. These findings support the idea that liver cell injury in experimental autoimmune hepatitis may at least in part be mediated by CTL.

Effects on interleukin 1 alpha and beta production of peripheral blood mononuclear cells from patients with hepatocellular carcinoma after transcatheter arterial embolization

To clarify the immunological effects of transcatheter arterial embolization (TAE) therapy for hepatocellular carcinoma (HCC), we investigated changes in the production of interleukin I (IL-I) alpha, as well as beta, determined by enzyme-linked immunosorbent assay (ELISA) before and after TAE therapy. Eleven patients with nonresectable HCC received intraarterial infusion chemotherapy and TAE using Gelfoam cubes. IL-I production was measured before and 7 days after TAE. Peripheral blood mononuclear cells obtained from patients were cultured in RPMI 1640 medium containing 10% fetal calf serum for 48 hr in the presence of lipopolysaccharide (I). Culture supernatants were recovered and assessed. IL-I alpha and beta were determined by ELISA (2,3). The amount of the sum of IL-I alpha and beta in the patients with HCC (1232 346 pg/ml;mean SD) was higher than that in healthy volunteers (968 159 pg/ml). Following one week of TAE, the sum of IL-I alpha and beta was significantly increased to 1804 903 pg/ml (p<0.05). Furthermore, the increase rate of IL-I beta from before to after TAE was significantly higher than that of IL-I alpha (p<0.05). The content of immunoreactive IL-I 2000 was increased after TAE, supporting the ~,L-f~ idea that TAE therapy may, at least ~,L-I~ ep<O.O5 in part, activate Kupffer cells and enhance immunological responses. These ~. immunomodulatory effects of TAE may influence therapeutic response. ~ooo

Molecular form of IgM antibody to hepatitis B core antigen in sera from the patients with chronic hepatitis B virus infection.

IgM型HBc抗体の分子性状を,B型肝炎ウイルスの一過性感染と持続感染で比較するとともに,持続感染において,その抗体価の変動に伴う分子性状の変化を検討した.その結果,一過性感染では急性期・回復期ともにその抗体活性は19S IgMのみに認められた.それに対し,持続感染では19S IgMばかりでなく7S IgMも抗体活性が認められた.さらに,持続感染ではIgM型HBc抗体が陰性時には7S IgMが主体であるが,急性増悪時など抗体陽性になる時にほ19S IgMが主体となっており,この様な分子性状の変化は同一症例でも確認された.つまり,持続感染例では急性肝炎と異なり7S IgMもIgM型HBc抗体活性を示すが,その急性増悪に際しては,19S成分のIgM型HBc抗体が増加すると考えられた.