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Induction of Airway Mucus Production By T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production

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TLDR
It is suggested that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.
Abstract
Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4–deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-α, IL-4 −/− Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

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Journal Article

Il-4-independent induction of airway hyperresponsiveness by th2, but not th1, cells

TL;DR: IL-4 production by Th2 cells is not essential for the induction of AHR, but is critical for the migration of eosinophils from lung tissue into the airways.
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Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3.

TL;DR: Targeting GATA-3 activity alone is sufficient to blunt Th2 responses in vivo, thereby establishing Gata-3 as a potential therapeutic target in the treatment of asthma and allergic diseases.
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IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development.

TL;DR: Deletion of IL-9 manifests as a highly defined phenotype in Th2 responses modulating mucus production and mast cell proliferation in response to lung challenge.
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Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation

TL;DR: Data indicate that Th2 cells require signals in addition to antigen for their effective recruitment to the airways, and Th1 cells can provide these signals.
References
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Journal Article

Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.

TL;DR: A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished.
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Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma

TL;DR: Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.
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Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens.

TL;DR: This paper used hybridoma monoclonal antibodies obtained after immunization of mice with rat cells to study rat cell-surface antigens present on subpopulations of rat lymphocytes.
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Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo

TL;DR: Results provide direct evidence for the in vivo role of apoptosis in the development of antigen-induced tolerance in mice transgenic for a T cell receptor that reacts to this peptide.
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Generation and analysis of interleukin-4 deficient mice.

TL;DR: Some but not all of the in vitro properties of IL-4 are critical for the physiology of the immune system in vivo, but the serum levels of IgG1 and IgE are strongly reduced.
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