In vivo function of an interleukin 2 receptor beta chain (IL-2Rbeta)/IL-4Ralpha cytokine receptor chimera potentiates allergic airway disease.

Youn J, Chen J, Goenka S, Aronica MA, Mora AL, Correa V, Sheller JR, Boothby M
J Exp Med. 1998 188 (10): 1803-16

PMID: 9815258 · PMCID: PMC2212401 · DOI:10.1084/jem.188.10.1803

Strength of T cell receptor (TCR) signaling, coreceptors, costimulation, antigen-presenting cell type, and cytokines all play crucial roles in determining the efficiency with which type 2 T lymphocytes (Th2, Tc2) develop from uncommitted precursors. To investigate in vivo regulatory mechanisms that control the population of type 2 T cells and disease susceptibility, we have created lines of transgenic mice in which expression of a chimeric cytokine receptor (the mouse interleukin 2 receptor beta chain [IL-2Rbeta] extracellular domain fused to the cytoplasmic tail of IL-4Ralpha) is targeted to the T lymphoid lineage using the proximal lck promoter. This chimera transduced IL-4-specific signals in response to IL-2 binding and dramatically enhanced type 2 responses (IL-4, IL-5, and immunoglobulin E production) upon in vitro TCR stimulation or in vivo antigen challenge. Thus, type 2 effector function was augmented by IL-4 signals transduced through a chimeric receptor expressed in a T cell-specific manner. This influence was sufficient for establishment of antigen-induced allergic airway hyperresponsiveness on a disease-resistant background (C57BL/6).

MeSH Terms (21)

Animals Asthma Bronchial Hyperreactivity Flow Cytometry Humans Hypersensitivity Immunization Immunoglobulin E Immunoglobulin G Methacholine Chloride Mice Mice, Transgenic Ovalbumin Receptors, Interleukin-2 Receptors, Interleukin-4 Recombinant Fusion Proteins Signal Transduction STAT6 Transcription Factor T-Lymphocytes Th2 Cells Trans-Activators

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