Interleukin-10-induced T cell unresponsiveness can be reversed by dendritic cell stimulation

Chen, Mao-Liang; Wang, Fu-Hwei; Lee, Pao-Kung; Lin, Ching-Yu

doi:10.1016/s0165-2478(00)00301-1

Cited by 20 publications

(10 citation statements)

References 23 publications

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“…First, the concomitant high levels of TNF-␣ and IL-10 induction by HCV core and NS3 proteins and observed in monocytes of HCVinfected patients suggest that TNF-␣ production in these patients may be resistant to the inhibitory effects of IL-10 (51). Second, IL-10 is a potent inhibitor of T cell activation and Ag-specific T cell proliferation, whose functions are reduced in chronic HCV (33,52). IL-10 has been shown to induce T cell anergy by specifically altering the CD28 costimulation pathway (53).…”

Section: Discussionmentioning

confidence: 99%

“…6, c and d), suggesting that cytokine abnormalities play a role in the altered allostimulatory capacity of DCs. IL-12 and IL-10 both have critical regulatory effects on T cell activation and proliferation (31)(32)(33). Thus, the role of reduced IL-12 and/or increased IL-10 in mediation of decreased allo-Ag-induced T cell proliferation with HCV core-and NS3-treated DCs was further evaluated.…”

Section: Figurementioning

confidence: 99%

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Hepatitis C Virus Core and Nonstructural Protein 3 Proteins Induce Pro- and Anti-inflammatory Cytokines and Inhibit Dendritic Cell Differentiation

Dolganiuc¹,

Kodys²,

Kopasz³

et al. 2003

The Journal of Immunology

229

215

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Antiviral immunity requires recognition of viral pathogens and activation of cytotoxic and Th cells by innate immune cells. In this study, we demonstrate that hepatitis C virus (HCV) core and nonstructural protein 3 (NS3), but not envelope 2 proteins (E2), activate monocytes and myeloid dendritic cells (DCs) and partially reproduce abnormalities found in chronic HCV infection. HCV core or NS3 (not E2) triggered inflammatory cytokine mRNA and TNF-α production in monocytes. Degradation of I-κBα suggested involvement of NF-κB activation. HCV core and NS3 induced production of the anti-inflammatory cytokine, IL-10. Both monocyte TNF-α and IL-10 levels were higher upon HCV core and NS3 protein stimulation in HCV-infected patients than in normals. HCV core and NS3 (not E2) inhibited differentiation and allostimulatory capacity of immature DCs similar to defects in HCV infection. This was associated with elevated IL-10 and decreased IL-2 levels during T cell proliferation. Increased IL-10 was produced by HCV patients’ DCs and by core- or NS3-treated normal DCs, while IL-12 was decreased only in HCV DCs. Addition of anti-IL-10 Ab, not IL-12, ameliorated T cell proliferation with HCV core- or NS3-treated DCs. Reduced allostimulatory capacity in HCV core- and NS3-treated immature DCs, but not in DCs of HCV patients, was reversed by LPS maturation, suggesting more complex DC defects in vivo than those mediated by core or NS3 proteins. Our results reveal that HCV core and NS3 proteins activate monocytes and inhibit DC differentiation in the absence of the intact virus and mediate some of the immunoinhibitory effects of HCV via IL-10 induction.

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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Hepatitis C Virus Core and Nonstructural Protein 3 Proteins Induce Pro- and Anti-inflammatory Cytokines and Inhibit Dendritic Cell Differentiation

Dolganiuc¹,

Kodys²,

Kopasz³

et al. 2003

The Journal of Immunology

229

215

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“…Finally, IL-10 plays a fundamental role in regulating MDSC functions; IL-10 together with TGF-b are considered the key factors released by the tumour (Chen et al 2001).…”

Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

Cellular and molecular pathways linking inflammation and cancer

et al. 2009

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“…12,13 It is also well established that T cells isolated from tumor tissue exhibit an anergic phenotype [14][15][16][17] and that such a phenotype can be induced in vitro in normal T cells exposed to inhibitory factors. 14,17,18 However, no direct evidence exists that the anergic phenotype observed in tumor infiltrating T cells is indeed due to exposure to inhibitory cytokines such as TGF␤, IL10, or PGE 2 . Moreover, there is not even direct evidence that these factors lead to signaling events within tumor-infiltrating T cells in vivo.…”

Section: Introductionmentioning

confidence: 99%

RNA fingerprints provide direct evidence for the inhibitory role of TGFβ and PD-1 on CD4+ T cells in Hodgkin lymphoma

Chemnitz

Eggle

Driesen

et al. 2007

Blood

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IntroductionTumors frequently develop evasion strategies that may influence every stage of the tumor-specific immune response, from the activation of antigen-presenting cells to T-cell recruitment, activation, and effector function. [1][2][3] Hodgkin lymphoma (HL) seems to be a role model for an ineffective tumor immune response, because the minority of tumor cells, so called Reed-Sternberg (RS) cells, are surrounded mainly by a mixture of reactive cells including lymphocytes, plasma cells, eosinophils, and histiocytes. 4,5 The majority of lymphocytes in close proximity to the tumor cells are CD4 ϩ T cells with anergic phenotype, indicating poor immune surveillance of the tumor. 6 In fact, several immune evasion strategies are described in HL, including down-regulation of immunodominant Epstein-Barr Virus (EBV) antigens, and secretion of soluble factors such as transforming growth factor beta (TGF␤), interleukin-10 (IL10), or prostaglandin E 2 (PGE 2 ), that have been shown to inhibit the activation of specific cytotoxic T lymphocytes (CTLs) and professional antigen-presenting cells in vitro and in murine models. [7][8][9][10] Also cell-to-cell interactions via inhibitory receptors might lead to immune inhibition. For example, neoplastic CD20 ϩ B cells in nodular lymphocyte-predominant HL express PDL-1, and the respective inhibitory receptor PD-1 is expressed by T cells in close proximity to the tumor cells. 11 So far, a general limitation studying immune inhibition within the tumor microenvironment, particularly in humans, is the fact that we rely solely on indirect evidence. This is best exemplified for soluble factors such as TGF␤, which is found to be elevated within the tumor microenvironment of many human tumors including lymphomas. 12,13 It is also well established that T cells isolated from tumor tissue exhibit an anergic phenotype [14][15][16][17] and that such a phenotype can be induced in vitro in normal T cells exposed to inhibitory factors. 14,17,18 However, no direct evidence exists that the anergic phenotype observed in tumor infiltrating T cells is indeed due to exposure to inhibitory cytokines such as TGF␤, IL10, or PGE 2 . Moreover, there is not even direct evidence that these factors lead to signaling events within tumor-infiltrating T cells in vivo.HL is a very good example for the existing circumstantial evidence. Activated lymphocytes, binucleate RS cells, and mononuclear Hodgkin cells have been described to express activated TGF␤. 7,13 The expression of TGF␤ as well as the functional phenotype of T cells in HL suggested that this cytokine might be involved in immunosuppression in HL, however, direct evidence is lacking. Other possible mechanisms of immune escape in HL might involve ligands for inhibitory receptors such as PDL-1 on the surface of the neoplastic cells. 11 PD-1 is a receptor of the Ig superfamily that negatively regulates T-cell antigen receptor signaling by interacting with the specific ligands (PDLs) and is suggested to play a role in the maintenance of self-tolerance. [19]...

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Interleukin-10-induced T cell unresponsiveness can be reversed by dendritic cell stimulation

Cited by 20 publications

References 23 publications

Hepatitis C Virus Core and Nonstructural Protein 3 Proteins Induce Pro- and Anti-inflammatory Cytokines and Inhibit Dendritic Cell Differentiation

Hepatitis C Virus Core and Nonstructural Protein 3 Proteins Induce Pro- and Anti-inflammatory Cytokines and Inhibit Dendritic Cell Differentiation

Cellular and molecular pathways linking inflammation and cancer

RNA fingerprints provide direct evidence for the inhibitory role of TGFβ and PD-1 on CD4+ T cells in Hodgkin lymphoma

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