Stimulation of Human CD4+ T Lymphocytes via TLR3, TLR5 and TLR7/8 Up-Regulates Expression of Costimulatory and Modulates Proliferation

Simone, Rita; Floriani, Antonio; Saverino, Danièle

doi:10.2174/1874285800903010001

Cited by 17 publications

(15 citation statements)

References 43 publications

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“…To date, the effects of R848 on T cell proliferation have mainly been investigated in the human system. R848 is able to induce T cell proliferation and activation of human CD4 + T cells (34); however, in MLRs, T cell proliferation was reduced after R848 application (35). In our in vivo system, proliferation of Ag-specific CD4 + T cells was likewise reduced suggesting that despite increased IFN-g, IFN-a, IFN-b, IL-12p35, IL-12p40, and KC in comparison with unsensitized but OVAchallenged controls is shown.…”

Section: Discussionmentioning

confidence: 56%

“…For intracellular cytokine analysis, we used allophycocyanin-labeled IFN-g (BD Pharmingen), PE-labeled IL-17A (BD Pharmingen), and PE-labeled IL-5 (BD Pharmingen). Abs were incubated at 4˚C for [30][31][32][33][34][35][36][37][38][39][40] ), single-cell suspensions of tracheal lymph nodes or lung cells were adjusted and surface stained for PeCy7-labeled CD4 PeCy7 and PE-labeled CD25 (all BD Pharmingen) as described. Foxp3 staining was performed following the advice of the manufacturer of the fixation/permeabilization set (eBioscience).…”

Section: Assessment Of Intracellular Cytokine Staining and Regulatorymentioning

confidence: 99%

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TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

Reuter¹,

Dehzad²,

Martin³

et al. 2012

The Journal of Immunology

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Epidemiological studies suggest that viral infections during childhood are a risk factor for the development of asthma. However, the role of virus-specific pattern recognition receptors in this process is not well defined. In the current study, we compare the effects of the inhaled viral TLR ligands polyinosinic-polycytidylic acid (TLR3) and resiquimod (TLR7/8) on sensitization to a model allergen (OVA) in a murine model. Both compounds enhance the migration, activation, and Ag-processing of myeloid dendritic cells from the lung to the draining lymph nodes comparable to the effects of LPS. Application of polyinosinic-polycytidylic acid [poly(I:C)] or LPS induces production of allergen-specific IgE and IgG1, whereas resiquimod (R848) had no effect. In addition, rechallenge of mice with OVA resulted in airway inflammation and mucus production in animals that received either poly(I:C) or LPS but not after application of R848. In summary, these results show that activation of TLR3 in combination with inhaled allergen results in induction of dendritic cell activation and migration similar to the effects of LPS. This leads to the development of allergic airway disease after allergen rechallenge, whereas mice treated with R848 did not develop allergic airway disease. These findings give further insight into the effects of stimulation of different TLRs on the development of asthma.

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Section: Discussionmentioning

confidence: 56%

Section: Assessment Of Intracellular Cytokine Staining and Regulatorymentioning

confidence: 99%

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

Reuter¹,

Dehzad²,

Martin³

et al. 2012

The Journal of Immunology

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“…As some studies previously demonstrated, direct TLR triggering on CD4 ϩ T cells can induce up-regulation of costimulatory molecules and modulate their proliferation. 48,49 Nevertheless, it has been demonstrated that the most effective multifunctional CD8 ϩ T-cell response is induced when the antigen is fused to the adjuvant, rather than delivered separately, 46 a finding that might explain the lack of CD8 ϩ T-cell responses in melanoma patients vaccinated with NY-ESO and topical TLR7 agonist. 50 Thus, our own data support the approach of conjugating TLR agonists to a targeting antigen vaccine, such as DCIR, as the most efficient method to deliver an antigen and adjuvant directly to DCs.…”

Section: Discussionmentioning

confidence: 99%

Cross-priming CD8+ T cells by targeting antigens to human dendritic cells through DCIR

Klechevsky

Flamar

Cao

et al. 2010

Blood

187

186

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We evaluated human CD8 ؉ T-cell responses generated by targeting antigens to dendritic cells (DCs) through various lectin receptors. We found the immunoreceptor tyrosine-based inhibitory motifcontaining DC immunoreceptor (DCIR) to mediate potent cross-presentation. A single exposure to a low dose of anti-DCIR-antigen conjugate initiated antigenspecific CD8 ؉ T-cell immunity by all human DC subsets including ex vivogenerated DCs, skin-isolated Langerhans cells, and blood myeloid DCs and plasma-

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“…In contrast, studies by others have shown costimulation of CD4+ T cells by dsRNA and LPS that are ligands of TLR3 and TLR4, respectively (Caramalho et al 2003;Gelman et al 2004). A recent study investigated the direct effects of TLR3, 5 and 7 ligands in regulating expression of costimulatory molecules on human peripheral CD4+ T cells (Simone et al 2009). Interestingly, stimulation of purified CD4+ T cells by each of the three (TLR3, 5 and 7) ligands resulted in reduced CD28 expression by 72 h poststimulation with a concurrent up-regulation of CD152 and PD-1 expression that inhibited further T cell proliferation and activation.…”

Section: Tlr-costimulation In Cd4+ T Cell Responsesmentioning

confidence: 99%

Insights into the role of Toll-like receptors in modulation of T cell responses

2010

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The innate immune receptors, such as Toll-like receptors (TLRs), are intimately involved in the early sensing of invading microorganisms or their structural components. Engagement of TLRs with their ligands results in activation of several downstream intracellular pathways leading to activation of innate and adaptive immune system cells. It was initially thought that TLRs are primarily expressed by antigen-presenting cells (APCs), such as macrophages and dendritic cells, and that interactions between microbial ligands and TLRs in these cells will indirectly result in activation of cells of the adaptive immune system, especially T cells. However, it has now become evident that TLRs are also expressed by various T cell subsets, such as conventional αβT cells, regulatory T cells, and γδT cells as well as natural killer T cells. Importantly, it appears that at least in some of these T cell subsets, TLRs are functionally active, because stimulation of these cells with TLR agonists in the absence of APCs results in exertion of effector or regulatory functions of T cells. The present review attempts to summarize the recent findings related to TLR expression in different T cell subsets and the direct role of TLRs in the induction and regulation of T cell responses, including those responses that occur at mucosal surfaces. In addition, the potential use of TLR agonists for steering T cell responses as a prophylactic or therapeutic strategy in the context of infectious, allergic or autoimmune diseases is explored.

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Stimulation of Human CD4+ T Lymphocytes via TLR3, TLR5 and TLR7/8 Up-Regulates Expression of Costimulatory and Modulates Proliferation

Cited by 17 publications

References 43 publications

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

Cross-priming CD8+ T cells by targeting antigens to human dendritic cells through DCIR

Insights into the role of Toll-like receptors in modulation of T cell responses

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