The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/11/1803/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 10, November 16, 1998 1803-1816

Articles

In Vivo Function of an Interleukin 2 Receptor β Chain (IL-2Rβ)/IL-4R{alpha} Cytokine Receptor Chimera Potentiates Allergic Airway Disease

Jeehee Youn*, Jin Chen{ddagger},§, Shreevrat Goenka*, Mark A. Aronica*,||, Ana L. Mora*, Victor Correa*, James R. Sheller||, and Mark Boothby*

From the * Department of Microbiology and Immunology, the {ddagger} Department of Cell Biology, and the § Rheumatology Division and || Pulmonary Division, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232

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 β chain [IL-2Rβ] extracellular domain fused to the cytoplasmic tail of IL-4R{alpha}) 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).

Key Words: interleukin 4 • T cell help • signal transduction • allergic diseases

Address correspondence to Mark Boothby, Department of Microbiology & Immunology, AA-4214B Medical Center North, Vanderbilt University Medical School, Nashville, TN 37232-2363. Phone: 615-343-1699; Fax: 615-343-9443; E-mail: mark.boothby{at}mcmail.vanderbilt.edu

2 Youn, J., et al., unpublished observations.

Abbreviations used: IRF, interferon regulatory factor; NTg, nontransgenic; Stat, signal transducer and activator of transcription;Tg, transgenic.


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