Presence of functional dendritic cells in patients chronically infected with hepatitis C virus

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 1026-1029 ◽  
Author(s):  
Randy S. Longman ◽  
Andrew H. Talal ◽  
Ira M. Jacobson ◽  
Matthew L. Albert ◽  
Charles M. Rice
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocytes ◽  
Memory T Cells ◽  
Immune Repertoire ◽  
Cd8 T Lymphocytes ◽  
Specific Memory ◽  
Chronic Hcv

Abstract The absence of expanded numbers of hepatitis C virus (HCV)-reactive CD8+ T lymphocytes (CTLs) in patients chronically infected with HCV has led to the investigation of dendritic cell (DC) function in this population as a potential cause for this defect. Several studies have shown evidence for impaired monocyte-derived DCs in chronically infected patients. As it is difficult to reconcile these data with the fact that patients with chronic HCV are immune competent, we re-evaluated this finding, carefully assessing phenotypic markers and functional activity of patient DCs as compared with noninfected controls. In contrast to these prior studies, DCs from 13 of 13 chronic HCV patients expressed typical maturation markers. These mature DCs were capable of priming allogeneic T lymphocytes, as well as stimulating influenza-specific memory T cells. This finding is consistent with clinical and immunologic data that the deficit in the patient's immune repertoire is HCV-specific and suggests that refined models are required for understanding the role of DCs in HCV pathogenesis. (Blood. 2004;103:1026-1029)

The role of hepatitis C virus specific CD4+ T lymphocytes in acute and chronic hepatitis C

1996 ◽  
Vol 74 (10) ◽  
pp. 583-588 ◽  
Author(s):  
H. M. Diepolder ◽  
R. Zachoval ◽  
R. M. Hoffmann ◽  
M.-C. Jung ◽  
T. Gerlach ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocytes ◽  
Chronic Hepatitis C ◽  
Acute And Chronic Hepatitis

Immune responses in hepatitis C virus infection: The role of dendritic cells

2003 ◽  
Vol 81 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Nina L Fowler ◽  
Joseph Torresi ◽  
David C Jackson ◽  
Lorena E Brown ◽  
Eric J Gowans
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Immune Responses ◽  
Hepatitis C Virus Infection

The role of cytotoxic T lymphocytes in hepatitis C virus (HCV) infection

1997 ◽  
Vol 56 ◽  
pp. 298
Author(s):  
N.B.C. Bovee ◽  
M.R. Klein ◽  
M. Damen ◽  
M. Beld ◽  
H.T.M. Cuypers ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Hcv Infection

scholarly journals Expression of hepatitis C virus-derived core or NS3 antigens in human dendritic cells leads to induction of pro-inflammatory cytokines and normal T-cell stimulation capabilities

2006 ◽  
Vol 87 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Wen Li ◽  
Jie Li ◽  
D. Lorne J. Tyrrell ◽  
Babita Agrawal
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Responses ◽  
The Body ◽  
Cell Responses ◽  
Core Proteins ◽  
Chronic Hcv

The majority of hepatitis C virus (HCV)-infected individuals become chronically infected, which can result in liver cirrhosis and hepatocellular carcinoma. Patients with chronic HCV are unable to prime and maintain vigorous T-cell responses, which are required to rid the body of the viral infection. Dendritic cells (DCs) are the professional antigen-presenting cells that probably play a dominant role in priming and maintaining vigorous T-cell responses in HCV infection. Furthermore, inefficient DC function may play an important role in HCV chronicity. In order to determine the effect of HCV NS3 and core proteins on phenotype and function of human DCs, recombinant adenoviral vectors containing NS3 or core genes were used to infect human DCs. HCV NS3- or core-protein expression in DCs was confirmed by Western blotting and immunofluorescence staining. The DCs expressing HCV NS3 or core proteins expressed several inflammatory cytokine mRNAs, had a normal phenotype and effectively stimulated allogeneic T cells, as well as T cells specific for another foreign antigen (tetanus toxoid). These findings are important for rational design of cellular-vaccine approaches for the immunotherapy of chronic HCV.

scholarly journals Cytotoxic T Lymphocytes Derived from Patients with Chronic Hepatitis C Virus Infection Kill Bystander Cells via Fas-FasL Interaction

2004 ◽  
Vol 78 (4) ◽  
pp. 2152-2157 ◽  
Author(s):  
Christel Gremion ◽  
Benno Grabscheid ◽  
Benno Wölk ◽  
Darius Moradpour ◽  
Jürg Reichen ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocytes ◽  
Virus Infection ◽  
Chronic Hepatitis C ◽  
Cytotoxic T Lymphocytes ◽  
Hepatitis C Virus Infection ◽  
Chronic Hepatitis C Virus

ABSTRACT The role of Fas-mediated lysis of hepatocytes in hepatitis C virus (HCV)-induced injury is frequently discussed. We therefore analyzed the effect of the number of HCV antigen-expressing cells, the mode of antigen presentation, and the number of cytotoxic T lymphocytes in a coculture system mimicking cellular components of the liver. Here, we show that endogenously processed HCV proteins are capable of inducing bystander killing. We further demonstrate that 0.8 to 1.5% of cells presenting HCV antigens suffice to induce lysis of 10 to 29% of bystander cells, suggesting that the mechanism may be operative at low fractions of infected versus uninfected hepatocytes in vivo. Our data underscore the role of the Fas pathway in HCV-related liver injury and support the exploration of Fas-based treatment strategies for patients with chronic hepatitis C virus infection.

scholarly journals Abnormal Priming of CD4+ T Cells by Dendritic Cells Expressing Hepatitis C Virus Core and E1 Proteins

2002 ◽  
Vol 76 (10) ◽  
pp. 5062-5070 ◽  
Author(s):  
Pablo Sarobe ◽  
Juan José Lasarte ◽  
Noelia Casares ◽  
Ascensión López-Díaz de Cerio ◽  
Elena Baixeras ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Interleukin 2 ◽  
T Cell Immunity ◽  
Cell Immunity ◽  
Chronic Hcv ◽  
Antigen Presenting

ABSTRACT Patients infected with hepatitis C virus (HCV) have an impaired response against HCV antigens while keeping immune competence for other antigens. We hypothesized that expression of HCV proteins in infected dendritic cells (DC) might impair their antigen-presenting function, leading to a defective anti-HCV T-cell immunity. To test this hypothesis, DC from normal donors were transduced with an adenovirus coding for HCV core and E1 proteins and these cells (DC-CE1) were used to stimulate T lymphocytes. DC-CE1 were poor stimulators of allogeneic reactions and of autologous primary and secondary proliferative responses. Autologous T cells stimulated with DC-CE1 exhibited a pattern of incomplete activation characterized by enhanced CD25 expression but reduced interleukin 2 production. The same pattern of incomplete lymphocyte activation was observed in CD4+ T cells responding to HCV core in patients with chronic HCV infection. However, CD4+ response to HCV core was normal in patients who cleared HCV after alpha interferon therapy. Moreover, a normal CD4+ response to tetanus toxoid was found in both chronic HCV carriers and patients who had eliminated the infection. Our results suggest that expression of HCV structural antigens in infected DC disturbs their antigen-presenting function, leading to incomplete activation of anti-HCV-specific T cells and chronicity of infection. However, presentation of unrelated antigens by noninfected DC would allow normal T-cell immunity to other pathogens.

Generation of hepatitis C virus‐specific cytotoxic T lymphocytes from healthy individuals with peptide‐pulsed dendritic cells

2001 ◽  
Vol 16 (3) ◽  
pp. 309-316 ◽  
Author(s):  
Akihiko Ito ◽  
Tatsuya Kanto ◽  
Noriyoshi Kuzushita ◽  
Tomohide Tatsumi ◽  
Yoshiko Sugimoto ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Healthy Individuals

scholarly journals Immunity in Chimpanzees Chronically Infected with Hepatitis C Virus: Role of Minor Quasispecies in Reinfection

1998 ◽  
Vol 72 (3) ◽  
pp. 1725-1730 ◽  
Author(s):  
Colby A. Wyatt ◽  
Linda Andrus ◽  
Betsy Brotman ◽  
Fannie Huang ◽  
Dong-Hun Lee ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Primary Infection ◽  
Hcv Infection ◽  
Natural Evolution ◽  
Genotype 1A ◽  
Natural Progression ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT We have previously reported that chimpanzees chronically infected with hepatitis C virus (HCV) could be reinfected, even with the original infecting strain. In this study we tested the hypothesis that this might reflect the presence of minor quasispecies to which there was little or no immunity. To evaluate this hypothesis, we sequenced multiple clones taken at intervals after primary infection and rechallenge from four chronically infected chimpanzees. The inoculum used in these studies (HCV-H, genotype 1a) revealed 17 separate variants among 46 clones sequenced. Following challenge, each of the four challenged animals showed marked alterations of their quasispecies distribution. The new variants, which appeared 1 to 6 weeks after challenge, were either identical to or closely resembled variants present in the challenge inoculum. These results, paralleled by an increase in viremia in some of the challenged animals, suggest that quasispecies in the challenge inoculum were responsible for signs of reinfection and that there was little immunity. However, the newly emerged quasispecies completely took over infection in only one animal. In the remaining three chimpanzees the prechallenge quasispecies were able to persist. The natural evolution of infection within chimpanzees resulted in variants able to compete with the inoculum variants. Whether through reexposure or the natural progression of infection, newly emerged quasispecies are likely to play a role in the pathogenesis of chronic HCV infection.

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