Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children

Freguja, Riccardo; Gianesin, Ketty; Mosconi, Ilaria; Zanchetta, Marisa; Carmona, Francesco; Rampon, Osvalda; Giaquinto, Carlo; Rossi, Anita De

doi:10.1111/j.1365-2249.2011.04383.x

Cited by 33 publications

(24 citation statements)

References 38 publications

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“…The majority of currently available data indicate that classical CD25 hi CD127 lo Treg are expanded during chronic progressive HIV-1 infection [32], [33], [34], [35], [36], [37] and may worsen spontaneous HIV-1 disease progression by potently suppressing functional activities of HIV-1-specific T cell responses [5], [17], [38]. Here, we demonstrate several numerical and functional aspects of non-classical HLA-G-expressing Treg in HIV-1 infection that clearly distinguish them from these recognized characteristics of classical Treg.…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of HLA-G+ Regulatory T Cells in HIV-1 Infection

Tóth

Wiesch

et al. 2013

PLoS Pathog

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Regulatory T cells represent a specialized subpopulation of T lymphocytes that may modulate spontaneous HIV-1 disease progression by suppressing immune activation or inhibiting antiviral T cell immune responses. While the effects of classical CD25hi FoxP3+ Treg during HIV-1 infection have been analyzed in a series of recent investigations, very little is known about the role of non-classical regulatory T cells that can be phenotypically identified by surface expression of HLA-G or the TGF-β latency-associated peptide (LAP). Here, we show that non-classical HLA-G-expressing CD4 Treg are highly susceptible to HIV-1 infection and significantly reduced in persons with progressive HIV-1 disease courses. Moreover, the proportion of HLA-G+ CD4 and CD8 T cells was inversely correlated to markers of HIV-1 associated immune activation. Mechanistically, this corresponded to an increased ability of HLA-G+ Treg to reduce bystander immune activation, while only minimally inhibiting the functional properties of HIV-1-specific T cells. Frequencies of LAP+ CD4 Treg were not significantly reduced in HIV-1 infection, and unrelated to immune activation. These data indicate an important role of HLA-G+ Treg for balancing bystander immune activation and anti-viral immune activity in HIV-1 infection and suggest that the loss of these cells during advanced HIV-1 infection may contribute to immune dysregulation and HIV-1 disease progression.

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Section: Discussionmentioning

confidence: 99%

Functional Characterization of HLA-G+ Regulatory T Cells in HIV-1 Infection

Tóth

Wiesch

et al. 2013

PLoS Pathog

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“…Some authors have found associations between Tregs, VL and immune activation at different disease stages [34,[57][58][59][60] …”

Section: Cd38mentioning

confidence: 99%

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Saison

Ferry

Demaret

et al. 2014

Clinical and Experimental Immunology

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SummaryThe mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (Tregs) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4 + T cell count (> or < 500/mm 3 ). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4 + lymphocytes, including Treg subsets, and CD8 + T cells was performed. Percentages of activated CD4 + T cells, Tregs, effector Tregs and terminal effector Tregs were found to be significantly elevated in iIR. Neither the percentage of activated CD8+ T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4 + T cell count and percentage of Tregs were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4 + and CD8+ T cells, Treg percentages and very low-level viraemia. Causative interactions between Tregs and CD4 + T cells should now be explored prospectively in a large patients cohort.

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“…In some conditions, innate tolerance is naturally prominent, or even essential, perhaps providing insights into new treatments for MS. Pregnancy, cancer, and HIV are all conditions in which a low-level tendency to activation of innate immunity is characteristically suppressed, and the immune system is reconfigured toward innate peripheral tolerance, leading to increased prevalence of Tregs [Trabanelli et al, 2011;Munn, 2011;Freguja et al, 2011]. In the physiological state of pregnancy, the readjustment is required to prevent rejection of a semiallogeneic fetus, whereas survival of cancerous cells (''altered self'') requires cancer cell-mediated immunosuppression.…”

Section: Enhancing Innate Tolerance As An Emerging Approach To Ms Thementioning

confidence: 98%

Innate origins of multiple sclerosis pathogenesis: Implications for computer‐assisted design of disease‐modifying therapies

Stoy

2011

Drug Development Research

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The rational development of disease-modifying therapies for multiple sclerosis (MS) requires a detailed knowledge of disease pathogenesis, but this remains incomplete. Dynamic computerassisted modeling of MS is currently hindered by uncertainties about the connectivity, compartmentalization, and dynamic sequencing of the components of the disease process. The present work presents a simple but versatile model of the mammalian immune system, incorporating both innate and adaptive immunity and innate and adaptive tolerance. The model is applied to MS and its animal model, experimental autoimmune encephalomyelitis (EAE), to interrogate the concept of initiation of MS lesions through activation of the peripheral innate immune system, triggering auto-reactive T cells against myelin antigens in the central nervous system (CNS). The model also addresses the modulation of proinflammatory neurotoxic responses by the generation of regulatory T cells (adaptive tolerance) and clarifies the role of innate tolerance, a part of the immune system that has been little explored in MS to date. Some ramifications of the model are mentioned, including its relevance to existing disease-modifying therapies and the need to look more closely at the innate immune system for future therapeutic targets. Drug Dev Res 72:674-688,

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Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children

Cited by 33 publications

References 38 publications

Functional Characterization of HLA-G+ Regulatory T Cells in HIV-1 Infection

Functional Characterization of HLA-G+ Regulatory T Cells in HIV-1 Infection

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Innate origins of multiple sclerosis pathogenesis: Implications for computer‐assisted design of disease‐modifying therapies

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