IN-VIVO FUNCTION OF AN INTERLEUKIN-2 RECEPTOR-BETA CHAIN (IL-2R-BETA)IL-4R-ALPHA CYTOKINE RECEPTOR CHIMERA POTENTIATES ALLERGIC AIRWAY DISEASE/

Strength of T cell receptor (TCR) signaling, coreceptors, costimulatio n, antigen-presenting cell type, and cytokines all play crucial Poles in determining the efficiency with which type 2 T lymphocytes (Th2, Tc 2) develop from uncommitted precursors. To investigate in vivo regulat ory mechanisms that control the population of type 2 T cells and disea se susceptibility, we have created lines of transgenic mice in which e xpression of a chimeric cytokine receptor (the mouse interleukin 2 rec eptor beta chain [IL-2R beta] extracellular domain fused to the cytopl asmic tail of IL-4R alpha) is targeted to the T lymphoid lineage using the proximal 1ck promoter. This chimera transduced IL-4-specific sign als in response to IL-2 binding and dramatically enhanced type 2 respo nses (IL-4, IL-5, and immunoglobulin E production) upon in vitro TCR s timulation or in vivo antigen challenge. Thus, type 2 effector functio n 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 hyperresponsivene ss on a disease-resistant background (C57BL/6).