Interleukin-15 production by monocyte-derived dendritic cells and T cell proliferation in HIV-infected patients with discordant response to highly active antiretroviral therapy

d’Ettorre, Gabriella; Forcina, Gabriele; Andreotti, Mauro; Sarmati, Loredana; Palmisano, Lucia; Andreoni, Massimo; Vella, Stefano; Mastroianni, Claudio Maria; Vullo, Vincenzo

doi:10.1111/j.1365-2249.2004.02373.x

Cited by 7 publications

(3 citation statements)

References 37 publications

(34 reference statements)

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“…Consistent with our results, partial restoration of other cytokines like IL-2 and IL-15 has also been observed in HIV-infected patients upon receiving HAART (36)(37)(38)(39).…”

Section: Discussionsupporting

confidence: 91%

Dynamics and Consequences of IL-21 Production in HIV-Infected Individuals: A Longitudinal and Cross-Sectional Study

Iannello

Boulassel

Samarani

et al. 2009

The Journal of Immunology

135

126

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IL-21 is a relatively newly discovered immune-enhancing cytokine that plays an essential role in controlling chronic viral infections. It is produced mainly by CD4+ T cells, which are also the main targets of HIV-1 and are often depleted in HIV-infected individuals. Therefore, we sought to determine the dynamics of IL-21 production and its potential consequences for the survival of CD4+ T cells and frequencies of HIV-specific CTL. For this purpose, we conducted a series of cross-sectional and longitudinal studies on different groups of HIV-infected patients and show in this study that the cytokine production is compromised early in the course of the infection. The serum cytokine concentrations correlate with CD4+ T cell counts in the infected persons. Among different groups of HIV-infected individuals, only elite controllers maintain normal production of the cytokine. Highly active antiretroviral therapy only partially restores the production of this cytokine. Interestingly, HIV infection of human CD4+ T cells inhibits cytokine production by decreasing the expression of c-Maf in virus-infected cells, not in uninfected bystander cells. We also show that the frequencies of IL-21–producing HIV-specific, but not human CMV-specific, Ag-experienced CD4+ T cells are decreased in HIV-infected viremic patients. Furthermore, we demonstrate in this study that recombinant human IL-21 prevents enhanced spontaneous ex vivo death of CD4+ T cells from HIV-infected patients. Together, our results suggest that serum IL-21 concentrations may serve as a useful biomarker for monitoring HIV disease progression and the cytokine may be considered for immunotherapy in HIV-infected patients.

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“…Consistent with our results, partial restoration of other cytokines like IL-2 and IL-15 has also been observed in HIV-infected patients upon receiving HAART (36)(37)(38)(39).…”

Section: Discussionsupporting

confidence: 91%

Dynamics and Consequences of IL-21 Production in HIV-Infected Individuals: A Longitudinal and Cross-Sectional Study

Iannello

Boulassel

Samarani

et al. 2009

The Journal of Immunology

135

126

View full text Add to dashboard Cite

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“…In addition to known perturbations of adaptive responses also innate immune responses are affected during human immunodeficiency virus (HIV)‐1 infection. Perturbations include reduced numbers and function of mDC [9,10,26,27], natural killer (NK) cell activation [28], decreased activating receptor expression and function [29], decreased interferon (IFN)‐γ and tumour necrosis factor‐α production [30] and increased NKG2C expression [31]. NK cells have editing functions on DCs [32] with potential effects on the shape of adaptive T and B cell responses, as they depend on DC for antigen presentation [27,33].…”

Section: Introductionmentioning

confidence: 99%

Conserved T cell and natural killer cell function in treatment-experienced adults receiving tenofovir plus didanosine as nucleoside reverse transcription inhibitor backbone

Costa

Bozzano²,

Fenoglio

et al. 2009

Clinical and Experimental Immunology

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Summary Anti-retroviral treatment (ART) usually results in efficient control of virus replication and in immune reconstitution. Among potential adverse effects, impairment of immune responses in terms of CD4+ T cell counts has been attributed to some ART regimens, as with didanosine-tenofovir. We studied the functional integrity of adaptive and innate immunity during didanosinetenofovir-containing ART. Two groups of extensively pretreated patients completing at least 48 weeks of ART containing either lamivudine-didanosine (n = 21) or tenofovir-didanosine (n = 25) were identified. In addition to standard clinical immune and virological parameters, we performed a flow cytometric analysis of natural killer (NK) cells, of memory and naive CD4+ T cells and of T cell receptor ab + T cells co-expressing inhibitory NK receptors. Functional analysis consisted in specific and total interferon-g production by NK cells and of recall antigen proliferation of peripheral blood mononuclear cells. Comparable clinical immunological reconstitution and virological control were confirmed in the two groups of patients in the absence of clinically relevant adverse effects. The proportion of CD4+ CD45RA + T cells and of functionally inhibited killer immunoglobulin-like receptor T cell receptor ab + cells, the proliferation to recall antigens as well as NK cell phenotype and function as determined by interferon-g production in patients treated with tenofovir-didanosine were comparable to those treated with a different regimen. Thus, no differences in functional innate or adaptive immune reconstitution are detected in drug-experienced human immunodeficiency virusinfected patients on tenofovir-didanosine nucleoside reverse transcription inhibitor regimens.

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“…Recent data suggest that lipopolysaccharide also induces IL‐15 production in human monocyte‐derived dendritic cells [58] and in epithelial cells [59]. Also, IL‐15 over expression increases susceptibility to lipopolysaccharide‐induced liver injury in BCG‐primed mice, via bystander activation of CD8 + T cells [60].…”

Section: A Role For Il‐15 In Virus‐induced Copdmentioning

confidence: 99%

Immunological pathways in virus‐induced COPD exacerbations: a role for IL‐15

Zdrenghea

Mallia

Johnston

2012

Eur J Clin Investigation

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Eur J Clin Invest 2012; 42 (9): 1010–1015 Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by high levels of antiviral type 1 cytokine interferon‐γ and activated CD8+ T cells. COPD exacerbations are the major cause of morbidity and mortality, have a prolonged and intense effect on quality of life and may result in accelerated loss of lung function. Respiratory virus infections, frequently within a state of colonization by bacteria, are the major cause of COPD exacerbations, and there is also evidence of virus latency in ‘stable’ disease, suggesting that latent infection might be a cause of chronic inflammation in COPD. Design This is an update of current literature concerning the role of interleukin‐15 and major histocompatibility complex class I‐related chain A and B molecules in type 1 immune responses, particularly to respiratory virus infections, which are the main cause of COPD exacerbations. We also present data from our own group suggesting a role for interleukin‐15 in virus‐induced COPD exacerbations. Results Type 1 cytokine interleukin‐15 is produced by resident airway cells (epithelial cells and macrophages) in response to virus infection and bacteria. Virus infections modulate major histocompatibility complex class I‐related chain A and B molecules in respiratory epithelial cells. Conclusions Interleukin‐15 could play a major role in the airway inflammation in COPD directly, via its own receptors, by amplifying the type 1 immune responses and decreasing apoptosis or indirectly, via modulating molecules associated with cytotoxic activity of natural killer and CD8+ T cells, such as major histocompatibility complex class I‐related chain A and B.

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Interleukin-15 production by monocyte-derived dendritic cells and T cell proliferation in HIV-infected patients with discordant response to highly active antiretroviral therapy

Cited by 7 publications

References 37 publications

Dynamics and Consequences of IL-21 Production in HIV-Infected Individuals: A Longitudinal and Cross-Sectional Study

Dynamics and Consequences of IL-21 Production in HIV-Infected Individuals: A Longitudinal and Cross-Sectional Study

Conserved T cell and natural killer cell function in treatment-experienced adults receiving tenofovir plus didanosine as nucleoside reverse transcription inhibitor backbone

Immunological pathways in virus‐induced COPD exacerbations: a role for IL‐15

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