Requirement for γδ T Cells in Allergic Airway Inflammation

Zuany-Amorim, Cláudia; Ruffié, Claude; Hailé, Solomon; Vargaftig, B. Boris; Pereira, Pablo; Pretolani, Marina

doi:10.1126/science.280.5367.1265

Cited by 257 publications

(226 citation statements)

References 13 publications

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“…1), as they do in vivo. Indeed, recent work in an allergic airway inflammation model that has pointed to the critical role of ␥␦ T cells in CD4 ϩ Th2 development, implying that these cells may serve as a source of IL-4, depending on the site and model of immunization (41). We emphasize that our studies have focused upon splenic ␥␦ T cells and that other subsets of these cells, for example those found at various epithelial surfaces, may have different phenotypes.…”

Section: Discussionmentioning

confidence: 95%

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Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Yin

Zhang

Welte³

et al. 2000

The Journal of Immunology

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γδ T cells secrete Th1- and Th2-like cytokines that help mediate innate and acquired immunity. We have addressed the mechanism whereby murine γδ T cells acquire the capacity to differentially produce such cytokines. Splenic γδ T cells could be polarized into IFN-γ- or IL-4-secreting cells in vitro; however, in contrast to CD4+ αβ T cells, γδ T cells predominantly produced IFN-γ, even in the presence of IL-4, a finding independent of genetic background. Like CD4+ Th1 cells, IFN-γ-producing cells expressed the IL-12 receptor β2-chain after activation in the presence of IL-12; however, unlike Th2 cells, IL-4-primed γδ T cells also expressed this receptor, even in the absence of IFN-γ and despite the presence of the transcription factor GATA-3. IL-12 also induced IL-4-primed γδ T cells to proliferate and to translocate Stat3/Stat4, indicating signaling through the IL-12 receptor. These molecular events can account for the predominant production of IFN-γ by γδ T cells in the presence of IL-12, despite the availability of IL-4. Early and predominant production of IFN-γ by γδ T cells likely is critical for the roles that these cells play in protection against intracellular pathogens and in tumor immunity.

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Section: Discussionmentioning

confidence: 95%

“…Th2 (IL-4) cytokines in vivo (23,24,26,40,41). The in vitro approach allowed us to identify fundamental differences in cytokine production between these two T cell lineages.…”

Section: Discussionmentioning

confidence: 99%

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Yin

Zhang

Welte³

et al. 2000

The Journal of Immunology

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“…Rather, the depletion of TCR␥␦ cells had an inhibitory effect in our discontinuous model, similar to its effect in the acute stages of allergic airway inflammation. 14,20 The maintenance of elevated serum IgE levels in the absence of airway inflammatory responses in continuous mice suggested that our inhalational tolerance was because of local mechanisms rather than systemic lymphocyte clonal deletion or anergy. If chronic OVA aerosol exposure had induced tolerance via clonal deletion or development of a dominant, antigen-specific, inhibitory T-cell population, tolerance should have been sustained with the absence of antigen or recalled with re-exposure.…”

Section: Discussionmentioning

confidence: 99%

Chronic Inhaled Ovalbumin Exposure Induces Antigen-Dependent but Not Antigen-Specific Inhalational Tolerance in a Murine Model of Allergic Airway Disease

Schramm

Puddington

et al. 2004

The American Journal of Pathology

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Sensitized mice acutely challenged with inhaled ovalbumin (OVA) develop allergic airway inflammation, characterized by OVA-specific IgE production, airway eosinophilia, increased pulmonary B and T lymphocytes, and airway hyperreactivity. In this study, a chronic exposure model was developed and two distinct patterns of response were observed. Discontinuous inhalational exposure to OVA (6 weeks) produced airway inflammation and hyperreactivity that were similar to acute (10 days) responses. Continuous inhalational exposure to OVA (6 or 11 weeks) resulted in attenuation of airway eosinophilia and hyperresponsiveness without reduction of OVA-specific IgE and IgG 1 levels. The inhibition of airway inflammation was dependent on continuous exposure to antigen, because continuously exposed mice with attenuated inflammatory responses redeveloped allergic airway disease if the OVA aerosols were interrupted and then restarted (11-week-discontinuous). Inhalational tolerance induced by continuous OVA exposure demonstrated bystander suppression of cockroach allergen-mediated airway eosinophilia. These findings may be attributed to changes in production of the anti-inflammatory cytokine interleukin-10 during continuous OVA aerosol exposure. The symptomatic and asymptomatic allergic responses in human asthmatics could be explained by similar variable or discontinuous exposures to aeroantigens. Throughout the past 40 years, the prevalence of allergic disease, including atopic dermatitis, hay fever, and asthma, has risen dramatically in the developed world. This disturbing trend is documented best for asthma. 1,2 A wealth of clinical and experimental data suggests that allergic asthma is due to an aberrant lung immune response mediated through T-helper type 2 cells (Th2 cells) and associated cytokine-signaling pathways. The normal lung is able to distinguish between airborne antigens associated with infectious agents, to which an immunological response is generated, and harmless inhaled antigens, which are usually ignored. In the asthmatic lung, some of these normally harmless antigens activate specific Th2 cells and elicit an inflammatory response characterized by Th2 cytokine production, eosinophilic airway inflammation, airway hyperresponsiveness, and bronchoconstriction. These pulmonary responses may be accompanied by systemic allergic sensitization, manifested by elevated titers of antigen-specific IgE. The mechanisms that control CD4 ϩ T lymphocyte polarization to allergenic Th2 phenotypes are incompletely understood but seem to involve genetic predispositions, local factors such as pre-existing cytokine concentrations and inflammation, and antigenic factors (ie, potency, dose, and duration of exposure).Several investigators have used mouse models to investigate the mechanisms of inhalational tolerance to antigens 3,4 or of allergic airway sensitization. [5][6][7][8][9][10] However, these responses have typically been assessed in isolation from each other. We have recently demonstrated that C57BL/6J mice undergo a biphasic...

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“…Zuany-Amorim et al (43) recently reported that early production of IL-4 by ␥␦ T cells is important for IgE response to OVA. It is reported that ␥␦ T cells express IL-12R␤1 after stimulation with IL-15 and produce IFN-␥ in response to IL-12 (40).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of IL-15 In Vivo Enhances Tc1 Response, Which Inhibits Allergic Inflammation in a Murine Model of Asthma

Ishimitsu

Nishimura

Yajima

et al. 2001

The Journal of Immunology

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IL-15, a pleiotropic cytokine, is involved in the inflammatory responses in various infectious and autoimmune diseases. We have recently constructed IL-15-transgenic (Tg) mice, which have an increased number of memory-type CD8+ T cells in the peripheral lymphoid tissues. In the present study, we found that eosinophilia and Th2-type cytokine production in the airway were severely attenuated in OVA-sensitized IL-15-Tg mice following OVA inhalation. IL-15-Tg mice preferentially developed Tc1 responses mediated by CD8+ T cells after OVA sensitization, and in vivo depletion of CD8+ T cells by anti-CD8 mAb aggravated the allergic airway inflammation in IL-15-Tg mice following OVA inhalation. Adoptive transfer of CD8+ T cells from OVA-sensitized IL-15-Tg mice into normal mice before OVA sensitization suppressed Th2 response to OVA in the normal mice. These results suggest that overexpression of IL-15 in vivo suppresses Th2-mediated-allergic airway response via induction of CD8+ T cell-mediated Tc1 response.

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Requirement for γδ T Cells in Allergic Airway Inflammation

Cited by 257 publications

References 13 publications

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Chronic Inhaled Ovalbumin Exposure Induces Antigen-Dependent but Not Antigen-Specific Inhalational Tolerance in a Murine Model of Allergic Airway Disease

Overexpression of IL-15 In Vivo Enhances Tc1 Response, Which Inhibits Allergic Inflammation in a Murine Model of Asthma

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