1991 Fiscal Year Final Research Report Summary
Immunopathology and therapy of chronic active hepatitis type B
| Project/Area Number |
01570402
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Kagawa Medical School |
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Principal Investigator |
NISHIOKA Mikio Kagawa Medical School, Undergraduate School of Medicine, Professor, 医学部, 教授 (30034937)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATSU Toshiaki Kagawa Medical School, School Hospital, Assistant, 医学部附属病院, 助手 (70198133)
ARIMA Keiji Kagawa Medical School, Undergraduate School of Medicine, Assistant, 医学部, 助手 (50212650)
WATANABE Seishiro Kagawa Medical School, School Hospital, Lecturer, 医学部附属病院, 講師 (00158635)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Hepatitis B virus / HB core antigen / Chronic active hepatitis / Natural killer cells / Lymphokine-activated killer cells / Anti-viral therapy / Interferon / Interleukin-2 |
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| Research Abstract |
Hepatitis B virus (HBV) may modify some immunological functions in patients with hepatitis B. In the present study, we have investigated the inhibitory effects of purified recombinant HBV surface antigen (rHBsAg) and core antigen (rHBcAg) on lymphokine-activated killer cell (LAK) activity in vitro. Peripheral blood mononuclear cells (PBMCs), which were preincubated with interleukin-2 (IL-2) or rHBsAg or rHBcAg for 72 hours, showed a significant decreased activity of LAK cells on cytotoxicity against Daudi cells. In contrast, both IL-2 with E. coli extracts and IL-2 alone demonstrated non-significant results. In addition, rHBsAg and rHBcAg showed depressed NK cell cytotoxicity against K562 cells. It is well known that NK and LAK cells play an important role in host immunosurveillance. Modification of immunosurveillance by HBV gene products may result in chronic HBV infection as well as hepatocellular carcinoma. The proliferation of PBMCs in response to rHBcAg was studied in patients wit
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h HBV infection. Significant proliferations of PBMCs to rHBcAg were detected in patients with acute hepatitis B as well as HBeAg positive chronic active hepatitis. A statistical correlation was found between proliferative responses of PBMCs and and serum transaminase levels. In proliferative response, CD4^+ cells responded well to rHBcAg in comparison to CD8^+ cells. The specific recognition of HBcAg by CD4^+ cells may play an important role in the clearance of HBV in humans. Our recent studies have revealed that HBcAg-specific enhancement mediated by CD4^+ cells and HBcAg-specific suppression mediated by CD8^+ cells are present even in the peripheral blood compartments in patients with chronic active hepatitis B, but not in HBs healthy carriers. Cell interactions between CD4 and CD8 in various stages of HBV infection may be responsible for the degree of hepatocellular injury. Treatment of chronic hepatitis B is still puzzling. However, recently, IL-2 therapy combined with interferon (IFN) alpha and combination therapy of IFN alpha and gamma have been applied for the last two years. Efficacy of these therapies are still under consideration, since duration of these therapies as well as follow-up was not satisfactory. Further studies are necessary to understand the enhancement of specific immune response to HBV clearing HBV-infected hepatocytes in humans. Less
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