Protective role of nuclear factor of activated T cells 2 in CD8+ long-lived memory T cells in an allergy model

Karwot, Roman; Maxeiner, Joachim; Schmitt, Steffen; Scholtes, Petra; Hausding, Michael; Lehr, Hans A.; Glimcher, Laurie H.; Finotto, Susetta

doi:10.1016/j.jaci.2007.12.1172

Cited by 30 publications

(27 citation statements)

References 28 publications

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“…However, we demonstrated in this study that CD8 ϩ CD122 ϩ and CD4 ϩ CD122 ϩ T cells are expanded in experimental asthma. Whereas the capacity of activated CD4 ϩ T cells to induce AHR in experimental asthma has been previously described, we recently found that depletion of CD8 ϩ CD122 ϩ T cells also significantly ameliorated AHR in a murine model of asthma (39). Collectively, these data indicate an important role for IL-2R ␤-chain signaling in controlling T cell function and AHR in experimental asthma.…”

Section: Foxp3supporting

confidence: 52%

IL-2 Receptor β-Chain Signaling Controls Immunosuppressive CD4+ T Cells in the Draining Lymph Nodes and Lung during Allergic Airway Inflammation In Vivo

Doganci

Karwot

Maxeiner

et al. 2008

The Journal of Immunology

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IL-2 influences both survival and differentiation of CD4+ T effector and regulatory T cells. We studied the effect of i.n. administration of Abs against the α- and the β-chains of the IL-2R in a murine model of allergic asthma. Blockade of the β- but not the α-chain of the IL-2R after allergen challenge led to a significant reduction of airway hyperresponsiveness. Although both treatments led to reduction of lung inflammation, IL-2 signaling, STAT-5 phosphorylation, and Th2-type cytokine production (IL-4 and IL-5) by lung T cells, IL-13 production and CD4+ T cell survival were solely inhibited by the blockade of the IL-2R β-chain. Moreover, local blockade of the common IL-2R/IL-15R β-chain reduced NK cell number and IL-2 production by lung CD4+CD25+ and CD4+CD25− T cells while inducing IL-10- and TGF-β-producing CD4+ T cells in the lung. This cytokine milieu was associated with reduced CD4+ T cell proliferation in the draining lymph nodes. Thus, local blockade of the β-chain of the IL-2R restored an immunosuppressive cytokine milieu in the lung that ameliorated both inflammation and airway hyperresponsiveness in experimental allergic asthma. These findings provide novel insights into the functional role of IL-2 signaling in experimental asthma and suggest that blockade of the IL-2R β-chain might be useful for therapy of allergic asthma in humans.

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Section: Foxp3supporting

confidence: 52%

IL-2 Receptor β-Chain Signaling Controls Immunosuppressive CD4+ T Cells in the Draining Lymph Nodes and Lung during Allergic Airway Inflammation In Vivo

Doganci

Karwot

Maxeiner

et al. 2008

The Journal of Immunology

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“…In a recent report, in a murine model of allergy, we identified a subpopulation of CD8 + T cells, the CD8 + CD122 + T-cell subpopulation, which is expanded in the absence of NFATc2 and selectively produces IL-10. We further showed in that report that the expansion of this CD8 + CD122 + T-cell population leads to the down-regulation of IL-2 production by the CD8 + NFATc2 (À/À) cells (21). Hence, NFATc2 expression in Fig.…”

Section: Discussionsupporting

confidence: 53%

“…+ T cells (20,21). As shown in + T cells compared with wild-type littermates, and the number of these cells was even further expanded in the lung of NFATc2 (À/À) mice bearing tumor.…”

Section: Resultsmentioning

confidence: 82%

A Key Regulatory Role of the Transcription Factor NFATc2 in Bronchial Adenocarcinoma via CD8+ T Lymphocytes

et al. 2009

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The Ca 2+ -regulated calcineurin/nuclear factor of activated T cells (NFAT) cascade controls alternative pathways of T-cell activation and peripheral tolerance. Here, we describe reduction of NFATc2 mRNA expression in the lungs of patients with bronchial adenocarcinoma. In a murine model of bronchoalveolar adenocarcinoma, mice lacking NFATc2 developed more and larger solid tumors than wild-type littermates. The extent of central tumor necrosis was decreased in the tumors in NFATc2

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“…The importance of IFN-g in the prevention of Th2-type pathologies was highlighted in several studies showing that one of the major factors associated with protection from allergic disorders is the ability of pathogens to induce strong IFN-g production by T cells (31,32). The IFN-g-dependent inhibitory effects of Th1-type CD4 + T cells on allergic airway eosinophilia and mucus production were described (33), and vaccination with Th1-directing adjuvants may activate CD4 + T cells to suppress the development of allergen-induced Th2-type responses (34).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Th2 Responses and Allergic Inflammation through Bystander Activation of CD8+ T Lymphocytes in Early Life

Dubois

Deruytter

Adams

et al. 2010

The Journal of Immunology

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Th2-biased immune responses characterizing neonates may influence the later onset of allergic disease. The contribution of regulatory T cell populations in the prevention of Th2-driven pathologies in early life is poorly documented. We investigated the potential of CD8+ T cells stimulated at birth with alloantigens to modulate the development of allergic airway inflammation. Newborn mice were immunized with semiallogeneic splenocytes or dendritic cells (DCs) and exposed at the adult stage to OVA aeroallergens. DC-immunized animals displayed a strong Th1 and Tc1/Tc2 alloantigen-specific response and were protected against the development of the allergic reaction with reduced airway hyperresponsiveness, mucus production, eosinophilia, allergen-specific IgE and IgG1, and reduction of lung IL-4, IL-5, IL-10, and IL-13 mRNA levels. By contrast, splenocyte-immunized mice displayed a Th2 and a weak Tc2 alloantigen-specific response and were more sensitive to the development of the allergen-specific inflammation compared with mice unexposed at birth to alloantigens. DC-immunized animals displayed an important increase in the percentage of IFN-γ–producing CD8+CD44high, CD8+CD62Lhigh, and CD8+CD25+ subsets. Adoptive transfers of CD8+ T cells from semiallogeneic DC-immunized animals to adult β2m-deficient animals prevented the development of allergic response, in particular IgE, IL-4, and IL-13 mRNA production in an IFN-γ–dependent manner, whereas transfers of CD8+ T cells from semiallogeneic splenocyte-immunized mice intensified the lung IL-4 and IL-10 mRNA level and the allergen-specific IgE. These findings demonstrated that neonatal induction of regulatory CD8+ T cells was able to modulate key parameters of later allergic sensitization in a bystander manner, without recognition of MHC class I molecules.

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Protective role of nuclear factor of activated T cells 2 in CD8+ long-lived memory T cells in an allergy model

Cited by 30 publications

References 28 publications

IL-2 Receptor β-Chain Signaling Controls Immunosuppressive CD4+ T Cells in the Draining Lymph Nodes and Lung during Allergic Airway Inflammation In Vivo

IL-2 Receptor β-Chain Signaling Controls Immunosuppressive CD4+ T Cells in the Draining Lymph Nodes and Lung during Allergic Airway Inflammation In Vivo

A Key Regulatory Role of the Transcription Factor NFATc2 in Bronchial Adenocarcinoma via CD8+ T Lymphocytes

Regulation of Th2 Responses and Allergic Inflammation through Bystander Activation of CD8+ T Lymphocytes in Early Life

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