1887

Journal of General Virology header logo

Volume 85, Issue 10

Phenotype and function of monocyte derived dendritic cells in chronic hepatitis B virus infection Free

Abstract

The antiviral T cell failure of patients with chronic hepatitis B virus (HBV) infection was suggested to be caused by a T cell stimulation defect of dendritic cells (DC). To address this hypothesis, monocyte derived DC (MDDC) of patients with chronic or resolved acute HBV infection and healthy controls were studied phenotypically by FACS analyses and functionally by mixed lymphocyte reaction, ELISA, ELISpot and proliferation assays of MDDC cultures or co-cultures with an allogeneic HBc-specific Th cell clone. HBV infection of MDDC was studied by quantitative PCR. MDDC from HBV patients seemed to be infected by the HBV, showed a reduced surface expression of HLA DR and CD40 and exhibited a reduced secretion of IL12p70 in response to HBcAg but not to LPS, as compared to control MDDC. However, after cytokine induced maturation, MDDC from HBV patients revealed an unimpaired phenotype. Moreover, the T cell stimulatory capacity of HBV-DC was intact, since (i) the induction of allospecific proliferative and IFN- responses was not affected in HBV-MDDC, and (ii) HLA DR7 restricted stimulation of an allogeneic HBc-specific Th cell clone was not impaired by HBV-MDDC compared to control MDDC. It is hypothesized that HBV infection of DC might lead to minor phenotypic and functional alterations without significantly affecting their antiviral Th cell stimulatory capacity.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80143-0
2004-10-01
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/10/vir852829.html?itemId=/content/journal/jgv/10.1099/vir.0.80143-0&mimeType=html&fmt=ahah

References

  1. Ahuja S. S., Mummidi S., Malech H. L., Ahuja S. K. 1998; Human dendritic cell (DC)-based anti-infective therapy: engineering DCs to secrete functional IFN-γ and IL-12. J Immunol 161:868–876
     [Google Scholar]
  2. Auffermann-Gretzinger S., Keeffe E. B., Levy S. 2001; Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection. Blood 97:3171–3176 [CrossRef]
     [Google Scholar]
  3. Bain C., Fatmi A., Zoulim F., Zarski J. P., Trepo C., Inchauspe G. 2001; Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology 120:512–524 [CrossRef]
     [Google Scholar]
  4. Banchereau J., Steinman R. M. 1998; Dendritic cells and the control of immunity. Nature 392:245–252 [CrossRef]
     [Google Scholar]
  5. Beckebaum S., Cicinnati V. R., Dworacki G. 8 other authors 2002; Reduction in the circulating pDC1/pDC2 ratio and impaired function of ex vivo -generated DC1 in chronic hepatitis B infection. Clin Immunol 104:138–150 [CrossRef]
     [Google Scholar]
  6. Bertoletti A., Ferrari C. 2003; Kinetics of the immune response during HBV and HCV infection. Hepatology 38:4–13
     [Google Scholar]
  7. Böcher W. O., Herzog-Hauff S., Schlaak J., Meyer zum Büschenfeld K. H., Löhr H. F. 1999; Kinetics of hepatitis B surface antigen-specific immune responses in acute and chronic hepatitis B or after HBs vaccination: stimulation of the in vitro antibody response by interferon- γ . Hepatology 29:238–244 [CrossRef]
     [Google Scholar]
  8. Chisari F. V., Ferrari C. 1995; Hepatitis B virus immunopathogenesis. Annu Rev Immunol 13:29–60 [CrossRef]
     [Google Scholar]
  9. Engelmayer J., Larsson M., Subklewe M., Chahroudi A., Cox W. I., Steinman R. M., Bhardwaj N. 1999; Vaccinia virus inhibits the maturation of human dendritic cells: a novel mechanism of immune evasion. J Immunol 163:6762–6768
     [Google Scholar]
  10. Hilkens C. M., Kalinski P., de Boer M., Kapsenberg M. L. 1997; Human dendritic cells require exogenous interleukin-12-inducing factors to direct the development of naive T-helper cells toward the Th1 phenotype. Blood 90:1920–1926
     [Google Scholar]
  11. Jonuleit H., Kuhn U., Muller G., Steinbrink K., Paragnik L., Schmitt E., Knop J., Enk A. H. 1997; Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol 27:3135–3142 [CrossRef]
     [Google Scholar]
  12. Jung M. C., Diepolder H. M., Spengler U. 7 other authors 1995; Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection. J Virol 69:3358–3368
     [Google Scholar]
  13. Kanto T., Hayashi N., Takehara T., Tatsumi T., Kuzushita N., Ito A., Sasaki Y., Kasahara A., Hori M. 1999; Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals. J Immunol 162:5584–5591
     [Google Scholar]
  14. Kunitani H., Shimizu Y., Murata H., Higuchi K., Watanabe A. 2002; Phenotypic analysis of circulating and intrahepatic dendritic cell subsets in patients with chronic liver diseases. J Hepatol 36:734–741 [CrossRef]
     [Google Scholar]
  15. Lew Y. Y., Michalak T. I. 2001; In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus. J Virol 75:1770–1782 [CrossRef]
     [Google Scholar]
  16. Löhr H. F., Pingel S., Böcher W. O., Bernhard H., Herzog-Hauff S., Rose-John S., Galle P. R. 2002; Reduced virus specific T helper cell induction by autologous dendritic cells in patients with chronic hepatitis B - restoration by exogenous interleukin-12. Clin Exp Immunol 130:107–114 [CrossRef]
     [Google Scholar]
  17. Macatonia S. E., Hosken N. A., Litton M. 7 other authors 1995; Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol 154:5071–5079
     [Google Scholar]
  18. Palucka K. A., Taquet N., Sanchez-Chapuis F., Gluckman J. C. 1998; Dendritic cells as the terminal stage of monocyte differentiation. J Immunol 160:4587–4595
     [Google Scholar]
  19. Randolph G. J., Beaulieu S., Lebecque S., Steinman R. M., Muller W. A. 1998; Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 282:480–483 [CrossRef]
     [Google Scholar]
  20. Randolph G. J., Inaba K., Robbiani D. F., Steinman R. M., Muller W. A. 1999; Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo . Immunity 11:753–761 [CrossRef]
     [Google Scholar]
  21. Romani N., Gruner S., Brang D. 7 other authors 1994; Proliferating dendritic cell progenitors in human blood. J Exp Med 180:83–93 [CrossRef]
     [Google Scholar]
  22. Servet-Delprat C., Vidalain P. O., Bausinger H., Manie S., Le Deist F., Azocar O., Hanau D., Fischer A., Rabourdin-Combe C. 2000; Measles virus induces abnormal differentiation of CD40 ligand-activated human dendritic cells. J Immunol 164:1753–1760 [CrossRef]
     [Google Scholar]
  23. Stoll-Becker S., Repp R., Glebe D., Schaefer S., Kreuder J., Kann M., Lampert F., Gerlich W. H. 1997; Transcription of hepatitis B virus in peripheral blood mononuclear cells from persistently infected patients. J Virol 71:5399–5407
     [Google Scholar]
  24. Trinchieri G., Scott P. 1994; The role of interleukin 12 in the immune response, disease and therapy. Immunol Today 15:460–463 [CrossRef]
     [Google Scholar]
  25. von Stebut E., Belkaid Y., Jakob T., Sacks D. L., Udey M. C. 1998; Uptake of Leishmania major amastigotes results in activation and interleukin 12 release from murine skin-derived dendritic cells: implications for the initiation of anti-Leishmania immunity. J Exp Med 188:1547–1552 [CrossRef]
     [Google Scholar]
  26. Wang F. S., Xing L. H., Liu M. X., Zhu C. L., Liu H. G., Wang H. F., Lei Z. Y. 2001; Dysfunction of peripheral blood dendritic cells from patients with chronic hepatitis B virus infection. World J Gastroenterol 7:537–541
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80143-0
Loading
Phenotype and function of monocyte derived dendritic cells in chronic hepatitis B virus infection
J. Gen. Virol. 85, 2829 (2004); https://doi.org/10.1099/vir.0.80143-0
/content/journal/jgv/10.1099/vir.0.80143-0
/content/journal/jgv/10.1099/vir.0.80143-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error