Different cytokine profiles of peripheral blood mononuclear cells from patients with persistent and self-limited hepatitis C virus infection

Sarih, M’hammed; Bouchrit, N; Benslimane, A.

doi:10.1016/s0165-2478(00)00210-8

Cited by 58 publications

(56 citation statements)

References 21 publications

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“…As a control, cells were left unstimulated or were treated with 5 g/ml HCV core protein. cell-mediated immunity (20,21) and Th2 cytokine dominance in the periphery of chronically infected patients (22,23). Extracellular HCV core is present in the livers of chronically infected HCV patients at sufficient quantities to cross-link gC1qR on APCs (19), resulting in dysregulation of host immunity and the establishment of viral persistence.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, chronically infected patients exhibit diminished virus-specific CTL responses (20,21) and a predominance of Th2 cytokines in the periphery early after infection (22,23). The use of HCV core-transgenic mice (24) or core-expressing recombinant vaccinia (25) and adenoviruses (26) has demonstrated a suppressive function for core protein, characterized by inhibition of T lymphocyte proliferation and Th1 cytokine (i.e., IL-2 and IFN-␥) production.…”

Section: Gc1q Receptor Ligation Selectively Down-regulates Human Il-1mentioning

confidence: 99%

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gC1q Receptor Ligation Selectively Down-Regulates Human IL-12 Production through Activation of the Phosphoinositide 3-Kinase Pathway

Waggoner

Cruise

Kassel

et al. 2005

The Journal of Immunology

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gC1qR, a complement receptor for C1q, plays a pivotal role in the regulation of inflammatory and antiviral T cell responses. Several pathogens, including hepatitis C virus, exploit gC1qR-dependent regulatory pathways to manipulate host immunity. However, the molecular mechanism(s) of gC1qR signaling involved in regulating inflammatory responses remains unknown. We report the selective inhibition of TLR4-induced IL-12 production after cross-linking of gC1qR on the surface of macrophages and dendritic cells. Suppression of IL-12 did not result from increased IL-10 or TGF-β, but was dependent on PI3K activation. Activation of PI3K and subsequent phosphorylation of Akt define an intracellular pathway mediating gC1qR signaling and cross-talk with TLR4 signaling. This is the first report to identify signaling pathways used by gC1qR-mediated immune suppression, and it establishes a means of complement-mediated immune suppression to inhibit Th1 immunity crucial for clearing pathogenic infection.

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Section: Discussionmentioning

confidence: 99%

Section: Gc1q Receptor Ligation Selectively Down-regulates Human Il-1mentioning

confidence: 99%

gC1q Receptor Ligation Selectively Down-Regulates Human IL-12 Production through Activation of the Phosphoinositide 3-Kinase Pathway

Waggoner

Cruise

Kassel

et al. 2005

The Journal of Immunology

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“…Suggested mechanisms by which HCV may alter host innate immunity involve the attenuation of IFN-␥ production by inhibited NK cells after the engagement of CD81 by the envelope protein E2 (5,34). This insufficient production of IFN-␥ could prevent the adaptive immune response from being skewed in favor of a Th1 inflammatory response (25,28). Supporting this hypothesis is the previous finding of enhanced T-cell apoptosis in patients with chronic HCV infections, which may down-regulate the cellular immune response and lead to infection persistence (32).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Apoptosis of Peripheral CD5-Negative B Lymphocytes from Chronically Hepatitis C Virus-Infected Patients: Reversal after Antiviral Treatment

Toubi¹,

Kessel²,

Peri³

et al. 2004

J Virol

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Whereas enhanced peripheral T-cell apoptosis and its association with autoimmunity have recently been reported, the apoptotic status of peripheral B cells in chronic hepatitis C virus (HCV) infection remains ambiguous. We therefore sought to investigate the sensitivity of peripheral B cells to apoptosis and to assess the possible benefits of antiviral treatment in mitigating these effects. Spontaneous apoptosis, the extent of apoptosis rescue, and NF-B expression in peripheral B cells were studied in patients with chronic HCV infections (group 1), in sustained responders after antiviral treatment (group 2), and in healthy controls (group 3). For group 1, spontaneous B-cell apoptosis was increased (26% ؎ 4.6%) and apoptosis rescue was altered (39%) compared to group 3 (18% ؎ 5% and 50%, respectively; P ‫؍‬ 0.001). In contrast, apoptosis and apoptosis rescue were similar for groups 2 and 3. Enhanced B-cell apoptosis was associated with decreased NF-B expression and was found only in CD5-negative (CD5 neg ) B cells, whereas CD5 pos cells were apoptosis resistant. Chronic HCV infection is associated with enhanced peripheral B-cell apoptosis and decreased apoptosis rescue. Successful antiviral treatment reverses these abnormalities to the levels seen in healthy individuals. The relative resistance of the CD5 pos B-cell subpopulation to apoptosis may play a role in HCV-related autoimmunity and lymphoproliferation.Hepatitis C virus (HCV) infection is considered to be the leading cause of chronic liver disease, with a prevalence rate of between 0.5 and 2% in Western countries and up to 10% in certain non-Western countries (12). The spontaneous resolution of chronic HCV infection is rare, suggesting that the virus actively evades the immune system and limits its ability to garner an effective response (2, 4). However, little is known about how this virus persists and whether its persistence is due to early innate or adaptive immune response alterations. It was recently and elegantly shown that the binding of the HCV envelope protein E2 to CD81 inhibits natural killer (NK) cell antiviral activity, allowing the persistence of HCV and the establishment of a chronic infection (5, 34). Although CD81 ligation by HCV E2 was demonstrated to costimulate T cells, members of our laboratory reported an enhanced level of peripheral T-cell apoptosis in chronic HCV infections and suggested that this increase could contribute to both viral persistence and disease severity (32). That study demonstrated a decreased expression of nuclear factor B (NF-B) in activated T cells of HCV-infected patients. Both enhanced apoptosis and decreased NF-B expression correlated with autoimmune markers such as circulating cryoglobulins and rheumatoid factor (RF). The pathogenetic link between HCV and B-cell lymphotropism in inducing both autoimmunity and lymphoproliferation is unclear The recent identification of the CD81 protein as one of the HCV receptor candidates on B lymphocytes (27) suggests a mechanism by which B cells are infected with or, alterna...

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“…They are also required for the maintenance of CD8 ϩ T-cell number and function (33). Clinical data indicate that patients who spontaneously clear viremia have stronger multiclonal Th1-based T-cell responses to HCV antigens than those who do not (45,49). Therefore, we analyzed the Th cell status of the immunized mice by measuring the cytokines released from the spleen cells after in vitro stimulation with HCV-specific peptides.…”

Section: Immunization With Vee/sin Particles Is Optimal For Elicitingmentioning

confidence: 99%

Induction of Broad CD4⁺and CD8⁺T-Cell Responses and Cross- Neutralizing Antibodies against Hepatitis C Virus by Vaccination with Th1-Adjuvanted Polypeptides Followed by Defective Alphaviral Particles Expressing Envelope Glycoproteins gpE1 and gpE2 and Nonstructural Proteins 3, 4, and 5

Lin¹,

Kwon²,

Polo³

et al. 2008

J Virol

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Broad, multispecific CD4؉ and CD8 ؉ T-cell responses to the hepatitis C virus (HCV), as well as viruscross-neutralizing antibodies, are associated with recovery from acute infection and may also be associated in chronic HCV patients with a favorable response to antiviral treatment. and CD8؉ T-cell responses to E1E2 and NS345 was obtained by first priming with Th1-adjuvanted proteins and then boosting with chimeric, defective alphaviruses expressing these HCV genes. In addition, this prime/ boost regimen resulted in the induction of anti-E1E2 antibodies capable of cross-neutralizing heterologous HCV isolates in vitro. This vaccine formulation and regimen may therefore be optimal in humans for protection against this highly heterogeneous global pathogen.

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Different cytokine profiles of peripheral blood mononuclear cells from patients with persistent and self-limited hepatitis C virus infection

Cited by 58 publications

References 21 publications

gC1q Receptor Ligation Selectively Down-Regulates Human IL-12 Production through Activation of the Phosphoinositide 3-Kinase Pathway

gC1q Receptor Ligation Selectively Down-Regulates Human IL-12 Production through Activation of the Phosphoinositide 3-Kinase Pathway

Enhanced Apoptosis of Peripheral CD5-Negative B Lymphocytes from Chronically Hepatitis C Virus-Infected Patients: Reversal after Antiviral Treatment

Induction of Broad CD4⁺and CD8⁺T-Cell Responses and Cross- Neutralizing Antibodies against Hepatitis C Virus by Vaccination with Th1-Adjuvanted Polypeptides Followed by Defective Alphaviral Particles Expressing Envelope Glycoproteins gpE1 and gpE2 and Nonstructural Proteins 3, 4, and 5

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Different cytokine profiles of peripheral blood mononuclear cells from patients with persistent and self-limited hepatitis C virus infection

Cited by 58 publications

References 21 publications

gC1q Receptor Ligation Selectively Down-Regulates Human IL-12 Production through Activation of the Phosphoinositide 3-Kinase Pathway

gC1q Receptor Ligation Selectively Down-Regulates Human IL-12 Production through Activation of the Phosphoinositide 3-Kinase Pathway

Enhanced Apoptosis of Peripheral CD5-Negative B Lymphocytes from Chronically Hepatitis C Virus-Infected Patients: Reversal after Antiviral Treatment

Induction of Broad CD4+and CD8+T-Cell Responses and Cross- Neutralizing Antibodies against Hepatitis C Virus by Vaccination with Th1-Adjuvanted Polypeptides Followed by Defective Alphaviral Particles Expressing Envelope Glycoproteins gpE1 and gpE2 and Nonstructural Proteins 3, 4, and 5

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Induction of Broad CD4⁺and CD8⁺T-Cell Responses and Cross- Neutralizing Antibodies against Hepatitis C Virus by Vaccination with Th1-Adjuvanted Polypeptides Followed by Defective Alphaviral Particles Expressing Envelope Glycoproteins gpE1 and gpE2 and Nonstructural Proteins 3, 4, and 5