Marking IL-4-producing cells by knock-in of the IL-4 gene

IL-4 is a cytokine which can be expressed by a number of cell types includi ng T(h)2 cells, mast cells and a population of CD4(+) NK1.1(+) NK T cells. Although phenotypic markers exist for identifying each of these cell types, there is at present no known cell surface marker common to all IL-4-produc ing cells. Using gene targeting in embryonic stem cells, we have modified t he IL-4 locus by knock-in of a transmembrane domain to generate mice that e xpress a membrane-bound form of IL-4 (mIL-4). Flow cytometry using an IL-4- specific mAb allowed the detection of IL-4-secreting T(h)2 cells, mast cell s and Nh T cells from mIL-4 mice. Furthermore, the analysis of immune respo nses in mIL-4 mice following immunization with anti-CD3 and anti-IgD has al lowed us to identify distinct subpopulations of IL-4-producing NK T cells, Thus, the expression of IL-4 in a membrane-bound form provides a novel meth od for the identification and characterization of IL-4-producing cells.