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Allostimulatory Capacity (allostimulatory + capacity)

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Medical Sciences	100%

Selected Abstracts

Additive Inhibition of Dendritic Cell Allostimulatory Capacity by Alcohol and Hepatitis C Is Not Restored by DC Maturation and Involves Abnormal IL-10 and IL-2 Induction

ALCOHOLISM, Issue 6 2003
Angela Dolganiuc
Background: Excessive alcohol use results in impaired immunity, and it is associated with increased incidence and progression of chronic hepatitis C virus (HCV) infection. Here we investigated the effects of HCV infection and alcohol on myeloid dendritic cells (DC) that are critical in antiviral immunity. Methods: Immature and mature DCs were generated from monocytes of chronic HCV infected patients (HCV-DC) and controls (N-DC) with IL-4 plus granulocyte-macrophage colony stimulating factor (GM-CSF) in the presence or absence of alcohol (25 mM). DC allostimulatory capacity was tested in mixed lymphocyte reaction (MLR) and cytokine production by ELISA. Results: Allostimulatory capacity of HCV-DCs was reduced compared to N-DCs and it was further inhibited by alcohol treatment (p < 0.01). MLR was also decreased with alcohol-treated N-DCs. DC phenotypic markers and apoptosis were comparable between HCV-DCs and N-DCs irrespective of alcohol treatment. However, HCV-DCs and alcohol-treated N-DCs exhibited elevated IL-10 and reduced IL-12 production. Reduced MLR with HCV-DCs and its further inhibition by alcohol coexisted with decreasing IL-2 levels (p < 0.017). DC maturation partially improved but failed to fully restore the reduced allostimulatory function of either alcohol-treated or alcohol-naïve HCV-DCs (p < 0.018). Conclusions: Alcohol and HCV independently and together inhibit DC allostimulatory capacity, increase IL-10, reduce IL-12 and IL-2 production that cannot be normalized by DC maturation. HCV and alcohol interact to modulate innate and adaptive immune responses via dendritic cells. [source]

B7-H1 up-regulation impairs myeloid DC and correlates with disease progression in chronic HIV-1 infection

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008
Xicheng Wang
Abstract Impaired myeloid dendritic cells (mDC) fail to elicit host antiviral immune responses, leading to disease progression in HIV-1 infection. However, mechanisms underlying mDC suppression remain elusive. In this study, we found that the T-cell co-stimulatory molecule programmed death-1 ligand-1 (B7-H1) is significantly up-regulated on peripheral mDC in HIV-1-infected typical progressors and AIDS patients, but is maintained at a relatively low level in long-term non-progressors. Successful immune reconstitution after highly active antiretroviral therapy, indicated by full suppression of HIV-1 replication and substantial increases of CD4 T-cell counts, correlated with a decrease in B7-H1 expression. Importantly, we also found that X4 HIV-1 isolates directly induced B7-H1 expression on mDC in vitro, while adding antiviral agents hampered this B7-H1 up-regulation. Blockade of B7-H1 in vitro strongly enhanced mDC-mediated allostimulatory capacity and IL-12 production. In contrast, B7-H1 ligation with soluble programmed death-1 (PD-1) reduced mDC maturation and IL-12 production but increased mDC apoptosis and IL-10 production. Thus, B7-H1 up-regulation may inhibit mDC-mediated immune response, thereby facilitating viral persistence and disease progression in HIV-1-infected patients. This study provides new evidence that B7-H1 inhibitory signaling may reversely mediate functional impairment of mDC in HIV-1 infection, which further supports the notion that B7-H1 blockade represents a novel therapeutic approach to this disease. [source]

Additive Inhibition of Dendritic Cell Allostimulatory Capacity by Alcohol and Hepatitis C Is Not Restored by DC Maturation and Involves Abnormal IL-10 and IL-2 Induction

Interferon-,2a is sufficient for promoting dendritic cell immunogenicity

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005
A. Tamir
Summary Type I interferons (IFNs) are widely used therapeutically. IFN-,2a in particular is used as an antiviral agent, but its immunomodulatory properties are poorly understood. Dendritic cells (DCs) are the only antigen-presenting cells able to prime naive T cells and therefore play a crucial role in initiating the adaptive phase of the immune response. We studied the effects of IFN-,2a on DC maturation and its role in determining Th1/Th2 equilibrium. We found that IFN-,2a induced phenotypic maturation of DCs and increased their allostimulatory capacity. When dendritic cells were stimulated simultaneously by CD40 ligation and IFN-,2a, the production of interleukin (IL)-10 and IL-12 was increased. In contrast, lipopolysaccharide (LPS) stimulation in the presence of IFN-,2a mainly induced IL-10 release. The production of IFN-, and IL-5 by the responder naive T cells was also amplified in response to IFN-,2a-treated DCs. Furthermore, IL-12 production by IFN-,2a-treated DCs was enhanced further in the presence of anti-IL-10 antibody. Different results were obtained when DCs were treated simultaneously with IFN-,2a and other maturation factors, in particular LPS, and then stimulated by CD40 ligation 36 h later. Under these circumstances, IFN-,2a did not modify the DC phenotype, and the production of IL-10/IL-12 and IFN-,/IL-5 by DCs and by DC-stimulated naive T cells, respectively, was inhibited compared to the effects on DCs treated with maturation factors alone. Altogether, this work suggests that IFN-,2a in isolation is sufficient to promote DC activation, however, other concomitant events, such as exposure to LPS during a bacterial infection, can inhibit its effects. These results clarify some of the in vivo findings obtained with IFN-,2a and have direct implications for the design of IFN-,-based vaccines for immunotherapy. [source]