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HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B

(1998) JOURNAL OF HEPATOLOGY. 28(1). p.8-16
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Abstract
Background/Aims: Hepatitis B virus specific T cell reponses are crucial for viral elimination but their nature is not fully understood. Methods: We studied the regulation of proliferation and cytokine production after antigenic stimulation in peripheral blood mononuclear cells from chronically HBV-infected patients and subjects with natural immunity after recovery from an acute infection, Proliferation and production of interferon-gamma, IL-10 and tumor necrosis factor-alpha were determined after stimulation with HBcAg, HBeAg or HBsAg in the absence or presence of IL-12 or neutralizing antibodies to IL-12, interferon-gamma, IL-4, IL-10 or tumor necrosis factor-alpha. Results: Upon stimulation with HBcAg or HBeAg, peripheral blood mononuclear cells from chronic hepatitis B virus patients displayed a clear class-II restricted proliferative response (SI greater than 2.5), Both interferon-gamma (less than 50 IU/ml) and IL-10 levels up to 600 pg/ml were detected, Proliferative or cytokine responses to HBsAg were very weak or absent, Addition of IL-12 to HBeAg-stimulated cultures increased the production of interferon-gamma to more than 200 IU/ml in all patients and slightly increased the production of IL-10, Neutralization of IL-10 increased the HBeAg-induced interferon-gamma production but had no effect on tumor necrosis factor-alpha production, Addition of anti-IL-4 or anti-tumor necrosis factor-alpha had no significant influence on proliferation or cytokine release, Importantly, in both chronic hepatitis B virus patients and naturally immune subjects, IL-12 induced proliferative and interferon-gamma responses in peripheral blood mononuclear cells stimulated with HBsAg. Conclusions: Our data indicate that peripheral blood mononuclear cells from chronic hepatitis B virus patients proliferate and produce interferon-gamma and IL-10 upon HBeAg but not upon HBsAg stimulation, IL-12 augments the HBeAg-induced responses and, additionally, provokes proliferation and interferon-gamma production in HBsAg-stimulated cultures.
Keywords
HBeAg, hepatitis B virus, HBsAg, interferon-gamma, interleukin-10, interleukin-12, T cell responses, BLOOD MONONUCLEAR-CELLS, ANTIGEN TRANSGENIC MICE, CELLULAR IMMUNE-RESPONSE, CD4(+) T-CELLS, VIRUS-INFECTION, CORE ANTIGEN, AUTOANTIBODY PRODUCTION, GAMMA PRODUCTION, IN-VITRO, TH1

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Citation

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Chicago
Vingerhoets, Johan, Peter Michielsen, Guido Vanham, Eugène Bosmans, Wilma Paulij, Albert Ramon, Paul Pelckmans, Luc Kestens, and Geert Leroux-Roels. 1998. “HBV-specific Lymphoproliferative and Cytokine Responses in Patients with Chronic Hepatitis B.” Journal of Hepatology 28 (1): 8–16.
APA
Vingerhoets, Johan, Michielsen, P., Vanham, G., Bosmans, E., Paulij, W., Ramon, A., Pelckmans, P., et al. (1998). HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B. JOURNAL OF HEPATOLOGY, 28(1), 8–16.
Vancouver
1.
Vingerhoets J, Michielsen P, Vanham G, Bosmans E, Paulij W, Ramon A, et al. HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B. JOURNAL OF HEPATOLOGY. 1998;28(1):8–16.
MLA
Vingerhoets, Johan, Peter Michielsen, Guido Vanham, et al. “HBV-specific Lymphoproliferative and Cytokine Responses in Patients with Chronic Hepatitis B.” JOURNAL OF HEPATOLOGY 28.1 (1998): 8–16. Print.
@article{176422,
  abstract     = {Background/Aims: Hepatitis B virus specific T cell reponses are crucial for viral elimination but their nature is not fully understood. 
Methods: We studied the regulation of proliferation and cytokine production after antigenic stimulation in peripheral blood mononuclear cells from chronically HBV-infected patients and subjects with natural immunity after recovery from an acute infection, Proliferation and production of interferon-gamma, IL-10 and tumor necrosis factor-alpha were determined after stimulation with HBcAg, HBeAg or HBsAg in the absence or presence of IL-12 or neutralizing antibodies to IL-12, interferon-gamma, IL-4, IL-10 or tumor necrosis factor-alpha. 
Results: Upon stimulation with HBcAg or HBeAg, peripheral blood mononuclear cells from chronic hepatitis B virus patients displayed a clear class-II restricted proliferative response (SI greater than 2.5), Both interferon-gamma (less than 50 IU/ml) and IL-10 levels up to 600 pg/ml were detected, Proliferative or cytokine responses to HBsAg were very weak or absent, Addition of IL-12 to HBeAg-stimulated cultures increased the production of interferon-gamma to more than 200 IU/ml in all patients and slightly increased the production of IL-10, Neutralization of IL-10 increased the HBeAg-induced interferon-gamma production but had no effect on tumor necrosis factor-alpha production, Addition of anti-IL-4 or anti-tumor necrosis factor-alpha had no significant influence on proliferation or cytokine release, Importantly, in both chronic hepatitis B virus patients and naturally immune subjects, IL-12 induced proliferative and interferon-gamma responses in peripheral blood mononuclear cells stimulated with HBsAg. 
Conclusions: Our data indicate that peripheral blood mononuclear cells from chronic hepatitis B virus patients proliferate and produce interferon-gamma and IL-10 upon HBeAg but not upon HBsAg stimulation, IL-12 augments the HBeAg-induced responses and, additionally, provokes proliferation and interferon-gamma production in HBsAg-stimulated cultures.},
  author       = {Vingerhoets, Johan and Michielsen, Peter and Vanham, Guido and Bosmans, Eug{\`e}ne and Paulij, Wilma and Ramon, Albert and Pelckmans, Paul and Kestens, Luc and Leroux-Roels, Geert},
  issn         = {0168-8278},
  journal      = {JOURNAL OF HEPATOLOGY},
  keyword      = {HBeAg,hepatitis B virus,HBsAg,interferon-gamma,interleukin-10,interleukin-12,T cell responses,BLOOD MONONUCLEAR-CELLS,ANTIGEN TRANSGENIC MICE,CELLULAR IMMUNE-RESPONSE,CD4(+) T-CELLS,VIRUS-INFECTION,CORE ANTIGEN,AUTOANTIBODY PRODUCTION,GAMMA PRODUCTION,IN-VITRO,TH1},
  language     = {eng},
  number       = {1},
  pages        = {8--16},
  title        = {HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B},
  url          = {http://dx.doi.org/10.1016/S0168-8278(98)80196-7},
  volume       = {28},
  year         = {1998},
}

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