Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness

Kumar, Ashok; Angel, Jonathan B.; Daftarian, M P; Parato, Karl; Cameron, D. William; Filion, Lionel G.; Díaz‐Mitoma, Francisco

doi:10.1046/j.1365-2249.1998.00689.x

Cited by 34 publications

(31 citation statements)

References 62 publications

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“…32 Earlier studies have demonstrated higher IL-10 production in HIV-1-infected monocytic cells in vitro, which may be of significance because of its ability to inhibit HIV replication and limit viral entry by downregulating the expression of chemokine receptors on T cells. 33 Thus, in the present study decreased expression of IL-6 and TNF-a by Tat C treatment could probably be associated with increased IL-10 production by Tat C.…”

Section: Discussionsupporting

confidence: 50%

Differential Effects of HIV Type 1 Clade B and Clade C Tat Protein on Expression of Proinflammatory and Antiinflammatory Cytokines by Primary Monocytes

Gandhi

Saiyed

Samikkannu

et al. 2009

AIDS Research and Human Retroviruses

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The existence of multiple subtypes of HIV-1 worldwide has created new challenges to control HIV-1 infection and associated neuropathogenesis. Previous studies indicate a difference in neuropathogenic manifestations of HIV-1-associated neuroAIDS between clade B-and clade C-infected subjects with clade B being more neuropathogenic than clade C. However, the exact mechanism underlying the differences in the neuropathogenesis by both the subtypes remains elusive. Development of neuroAIDS is associated with a complex interplay between proinflammatory and antiinflammatory cytokines and chemokines. In the current study, we hypothesize that HIV-1 clade B and C Tat protein exert differential effects on human primary monocytes leading to differences in gene and protein expression of cytokines implicated in neuroAIDS. Primary human monocytes were treated with clade B and clade C Tat protein and quantitative real time PCR was performed to determine gene expression of proinflammatory cytokines (IL-6 and TNF-a) and antiinflammatory cytokines (IL-4 and IL-10). Further, cytokine secretion was measured in culture supernatants by ELISA, whereas intracellular cytokine expression was detected by flow cytometry. Results indicate that monocytes treated with Tat B showed significant upregulation of proinflammatory cytokines, IL-6 and TNF-a, as compared to Tat C-treated cultures. However, expression of antiinflammatory molecules and IL-4 and IL-10 was found to be higher in Tat C-treated compared to Tat B-treated cultures. Thus, our result shows for the first time that Tat B and Tat C differentially modulate expression of neuropathogenic molecules that may be correlated with the differences in neuroAIDS manifestation induced by clade-specific infections.

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Section: Discussionsupporting

confidence: 50%

Differential Effects of HIV Type 1 Clade B and Clade C Tat Protein on Expression of Proinflammatory and Antiinflammatory Cytokines by Primary Monocytes

Gandhi

Saiyed

Samikkannu

et al. 2009

AIDS Research and Human Retroviruses

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“…The supernatants were frozen at Ϫ70°C and thawed at the time of analysis. IL-10 levels were measured by enzyme-linked immunosorbent assay by using two different monoclonal antibodies that recognize distinct epitopes, as described (17,40).…”

Section: Methodsmentioning

confidence: 99%

“…Flow Cytometric Analysis-Cells were subjected to flow cytometric analysis as described (17,40). Briefly, cells were stained with 3 l of fluorescein isothiocyanate-labeled anti-CD14 monoclonal antibodies (Becton Dickinson) along with isotype (IgG2b)-matched control antibodies (Becton Dickinson).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, IL-10 knockout mice demonstrate a state of chronic inflammation (12), severe disease in experimental allergic encephalomyelitis (13), and bronchopulmonary aspergillosis (14), suggesting that IL-10 plays a beneficial role in controlling the harmful inflammatory response in these conditions. In humans, high levels of IL-10 have been shown to be produced in patients with HIV infection (17)(18)(19) and in septic shock (20). There is also evidence to suggest that polymorphism in the hIL-10 promoter region is associated with altered IL-10 expression in autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus (21).…”

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confidence: 99%

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The p38 Mitogen-activated Kinase Pathway Regulates the Human Interleukin-10 Promoter via the Activation of Sp1 Transcription Factor in Lipopolysaccharide-stimulated Human Macrophages

Ma¹,

Lim²,

Gee³

et al. 2001

Journal of Biological Chemistry

291

293

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Interleukin-10 (IL-10), a pleiotropic cytokine that inhibits inflammatory and cell-mediated immune responses, is produced by a wide variety of cell types including T and B cells and monocytes/macrophages. Regulation of pro-and anti-inflammatory cytokines has been suggested to involve distinct signaling pathways. In this study, we investigated the regulation of the human IL-10 (hIL-10) promoter in the human monocytic cell line THP-1 following activation with lipopolysaccharide (LPS). Analysis of hIL-10 promoter sequences revealed that DNA sequences located between base pairs ؊652 and ؊571 are necessary for IL-10 transcription. A computer analysis of the promoter sequence between base pairs ؊652 and ؊571 revealed the existence of consensus sequences for Sp1, PEA1, YY1, and EpsteinBarr virus-specific nuclear antigen-2 (EBNA-2)-like transcription factors. THP-1 cells transfected with a plasmid containing mutant Sp1 abrogated the promoter activity, whereas plasmids containing the sequences for PEA1, YY1, and EBNA-2-like transcription factors did not influence hIL-10 promoter activity. To understand the events upstream of Sp1 activation, we investigated the role of p38 and extracellular signal-regulated kinase mitogenactivated protein kinases by using their specific inhibitors. SB202190 and SB203580, the p38-specific inhibitors, inhibited LPS-induced IL-10 production. In contrast, PD98059, a specific inhibitor of extracellular signal-regulated kinase kinases, failed to modulate IL-10 production. Furthermore, SB203580 inhibited LPS-induced activation of Sp1, as well as the promoter activity in cells transfected with a plasmid containing the Sp1 consensus sequence. These results suggest that p38 mitogen-activated protein kinase regulates LPS-induced activation of Sp1, which in turn regulates transcription of the hIL-10 gene.

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“…IL-10 producing HIV-specific CD4 ϩ regulatory T cells suppressed both CD4 ϩ and CD8 ϩ HIV-specific T cell function in vitro (14 -16). Previous studies have found that the proliferation of CD4 ϩ T cells from HIV-infected individuals was inversely associated with the levels of IL-10 and that responses were partially restored by anti-IL-10 Abs (17,18). In addition, a higher frequency of CD4 ϩ T cells producing IL-10 was associated with a more progressive HIV disease (19).…”

mentioning

confidence: 97%

HIV-Specific IL-10-Positive CD8+ T Cells Suppress Cytolysis and IL-2 Production by CD8+ T Cells

Elrefaei

Ventura

Baker

et al. 2007

The Journal of Immunology

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IL-10 producing T cells inhibit Ag-specific CD8+ T cell responses and may play a role in the immune dysregulation observed in HIV infection. We have previously observed the presence of HIV-specific IL-10-positive CD8+ T cells in advanced HIV disease. In this study, we examined the suppressive function of the Gag-specific IL-10-positive CD8+ T cells. Removal of these IL-10-positive CD8+ T cells resulted in increased cytolysis and IL-2, but not IFN-γ, production by both HIV- and human CMV-specific CD8+ T cells. In addition, these IL-10-positive CD8+ T cells mediated suppression through direct cell-cell contact, and had a distinct immunophenotypic profile compared with other regulatory T cells. We describe a new suppressor CD8+ T cell population in advanced HIV infection that may contribute to the immune dysfunction observed in HIV infection.

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Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness

Cited by 34 publications

References 62 publications

Differential Effects of HIV Type 1 Clade B and Clade C Tat Protein on Expression of Proinflammatory and Antiinflammatory Cytokines by Primary Monocytes

Differential Effects of HIV Type 1 Clade B and Clade C Tat Protein on Expression of Proinflammatory and Antiinflammatory Cytokines by Primary Monocytes

The p38 Mitogen-activated Kinase Pathway Regulates the Human Interleukin-10 Promoter via the Activation of Sp1 Transcription Factor in Lipopolysaccharide-stimulated Human Macrophages

HIV-Specific IL-10-Positive CD8+ T Cells Suppress Cytolysis and IL-2 Production by CD8+ T Cells

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