J. Exp. Med., Volume 188, Number 10, November 16, 1998 1803-1816

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

By Jeehee Youn,^* Jin Chen,^§ Shreevrat Goenka,^* Mark A. Aronica,^* Ana L. Mora,^* Victor Correa,^* James R. Sheller, and Mark Boothby^*

From the ^* Department of Microbiology and Immunology, the  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  chain [IL-2R] extracellular domain fused to the cytoplasmic tail of IL-4R) 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).

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