Serum Interleukin-6 (IL-6), IL-10, Tumor Necrosis Factor (TNF) Alpha, Soluble Type II TNF Receptor, and Transforming Growth Factor Beta Levels in Human Immunodeficiency Virus Type 1-Infected Individuals with<i>Mycobacterium avium</i>Complex Disease

Havlir, Diane V.; Torriani, Francesca J.; Schrier, Rachel; Huang, Jenny; Lederman, Michael M.; Chervenak, Keith; Boom, W. Henry

doi:10.1128/jcm.39.1.298-303.2001

Cited by 27 publications

(27 citation statements)

References 22 publications

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“…In support of this mechanism, we found that, prior to ART, the amount of CD4 + T cell proliferation negatively correlated with the frequency of CTLA-4 + PD-1 − memory CD4 + T cells in the LN, suggesting that this CTLA-4 subset expands to reduce immune activation in the absence of ART. Moreover, HIV infection leads to changes in several cytokines that can influence the differentiation and survival of Treg cells, including IL-2, TGF-β, TNF-α, and IL-1 (Havlir et al, 2001; Orsilles et al, 2006). Thus, changes in the number and susceptibility to infection of Treg cells could also result from the increased inflammatory cytokine environment associated with HIV replication.…”

Section: Discussionmentioning

confidence: 99%

CTLA-4+PD-1− Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques

et al. 2017

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Summary Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals, but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1+ follicular helper T cells (Tfh) as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4+PD-1− memory CD4+ T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV-DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus. In contrast to PD-1+ Tfh, SIV-enriched CTLA-4+PD-1− CD4+ T cells were found outside the B-cell follicle of the LN, predicted the size of the persistent viral reservoir during ART, and significantly increased their contribution to the SIV reservoir with prolonged ART-mediated viral suppression. We have shown that CTLA-4+PD-1− memory CD4+ T cells are a previously unrecognized component of the SIV and HIV reservoir that should be therapeutically targeted for a functional HIV-1 cure.

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Section: Discussionmentioning

confidence: 99%

CTLA-4+PD-1− Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques

et al. 2017

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“…As such, the physiological consequences of this may be more pronounced than those observed in vitro. Other soluble cytokine receptors known to be produced at similar concentrations in vivo include sTNFR with concentrations approaching 2000 ng/ml (35), and up to 75 ng/ml of IL-6R has been detected in the sera of HIV + individuals (36). However, comparably lower concentrations of sIL2Ra (6 ng/ml) were measured in the serum of patients with MS, yet these concentrations were able to inhibit IL-2 activity in vitro (37).…”

Section: Discussionmentioning

confidence: 99%

Soluble IL-7Rα (sCD127) Inhibits IL-7 Activity and Is Increased in HIV Infection

Crawley

Faucher

Angel

2010

The Journal of Immunology

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Soluble CD127 (sCD127) appears to play an important role in the immunopathogenesis of several chronic infections, multiple sclerosis, and various cancers. The function of sCD127 and whether it influences IL-7 bioavailability or activity is unknown. In this study, we demonstrated that recombinant and native sources of sCD127 significantly inhibited IL-7–mediated STAT5 and Akt phosphorylation in CD8+ T cells. IL-7–mediated proliferation and Bcl-2 expression were similarly reduced by sCD127. In each case, native sCD127 inhibited IL-7 activity to a greater degree than rsCD127. Anti–IL-7 activity was inherent to human plasma and could be reversed by depletion of CD127, revealing for the first time the biological activity of naturally occurring sCD127. Plasma sCD127 concentrations were increased in HIV+ individuals compared with HIV− controls, correlated with IL-7 levels, and remained unchanged in HIV+ individuals following 1 y of effective antiretroviral therapy. Determining the regulation and function of sCD127 may be critical for understanding both the pathogenesis of diseases in which IL-7 likely has a role (e.g., HIV infection, cancer) and its potential impact on IL-7 as a therapeutic approach.

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“…Numerous studies have shown that TGF␤ levels were elevated during HIV infection and were associated with disease progression (16)(17)(18). Titers of plasma TGF␤ were shown to be sufficient to induce cellular responses in vitro (16).…”

Section: Hronic Human Immunodeficiency Virus (Hiv) Infection Ismentioning

confidence: 99%

Suppression of Transforming Growth Factor β Receptor 2 and Smad5 Is Associated with High Levels of MicroRNA miR-155 in the Oral Mucosa during Chronic Simian Immunodeficiency Virus Infection

George

Lewis

Renne

et al. 2015

J Virol

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C hronic human immunodeficiency virus (HIV) infection is characterized by a significant increase in generalized immune activation (1, 2) and in mucosal inflammatory conditions such as periodontitis and gingivitis (3-6). Some studies have reported an increased migration of inflammatory cells into the oral mucosa (7), whereas others have shown that levels of proinflammatory cytokines such as interleukin-6 (IL-6) (8-10) were significantly elevated during HIV infection. Interestingly, chronic immune activation and mucosal inflammation occurs in the presence of transforming growth factor ␤ (TGF␤), a highly immunosuppressive cytokine (11, 12) that has been shown to deactivate mononuclear phagocytes (13), reduce IL-2 receptor expression on T cells, and inhibit IL-2-induced T cell proliferation (14,15).Numerous studies have shown that TGF␤ levels were elevated during HIV infection and were associated with disease progression (16-18). Titers of plasma TGF␤ were shown to be sufficient to induce cellular responses in vitro (16). Likewise, simian immunodeficiency virus (SIV)-infected rhesus macaques were found to have persistently increased levels of TGF␤ in the plasma during chronic infection (19).Why immune activation and chronic inflammation persist even in the presence of high levels of immunosuppressive cytokines is not clear. Ploquin et al. (20) reported that the failure of TGF␤ to resorb virus-driven inflammation and activation during pathogenic HIV type 1 (HIV-1) and SIV infections may be due to increased unresponsiveness to TGF␤ that was associated with altered signaling. The exact mechanisms for this unresponsiveness are still not clear.TGF␤ binds to and signals through its high-affinity type I and type II serine/threonine kinase receptors TGF␤ receptor 1 (TGF␤-R1) and TGF␤-R2, which are expressed on a variety of cell types (21,22). Binding of TGF␤ to TGF␤-R2 phosphorylates and activates TGF␤-R1, which in turn recruits and phosphorylates a number of receptor-activated Smad proteins such as Smad1 to Smad5 (23). We hypothesized that the inability of TGF␤ to suppress immune activation may be associated with the dysregulated expression of its receptors in the oral mucosa. The loss of TGF␤ receptors has been shown to mediate resistance to TGF␤ in cell lines (22,24). We used the rhesus macaque model of HIV infection to address this question.Seventeen rhesus macaques (Macaca mulatta) of Indian origin (n ϭ 17) were used in this study. Ten animals were chronically infected with pathogenic SIVmac251, whereas the rest (n ϭ 7) were uninfected. The animals were housed in accordance with the guidelines of the American Association for Accreditation of Laboratory Animal and were seronegative for SIV, simian retrovirus (SRV), and simian T-cell leukemia virus (STLV) type 1 prior to SIV challenge.Peripheral blood and oropharyngeal tissue samples were collected at the time of sacrifice. Plasma and peripheral blood mononuclear cells (PBMC) were isolated and cryopreserved along with the oropharyngeal tissue samples. PBMC were isolated...

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Serum Interleukin-6 (IL-6), IL-10, Tumor Necrosis Factor (TNF) Alpha, Soluble Type II TNF Receptor, and Transforming Growth Factor Beta Levels in Human Immunodeficiency Virus Type 1-Infected Individuals withMycobacterium aviumComplex Disease

Cited by 27 publications

References 22 publications

CTLA-4+PD-1− Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques

CTLA-4+PD-1− Memory CD4+ T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques

Soluble IL-7Rα (sCD127) Inhibits IL-7 Activity and Is Increased in HIV Infection

Suppression of Transforming Growth Factor β Receptor 2 and Smad5 Is Associated with High Levels of MicroRNA miR-155 in the Oral Mucosa during Chronic Simian Immunodeficiency Virus Infection

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