The relationship of IL-4- and IFN gamma-producing T cells studied by lineage ablation of IL-4-producing cells.

Subsets of CD4 T cells are defined by the cytokines that they produce; these cytokines determine the effector function of these cells. Cloned CD4 T cells fall into two subsets, producing either interferon-gamma (IFN gamma) or interleukin-4 (IL-4) in combination with other cytokines, and are called Th1 and Th2 cells, respectively. The lineage relationship between naive T cells and effector Th1- and Th2-type cells is unclear. We generated transgenic mice in which IL-4-producing cells express herpes simplex virus 1 thymidine kinase and are eliminated by ganciclovir (GANC). Activation of transgenic T cells in the presence of GANC eliminates IL-4 and IFN gamma production, showing that IL-4- and IFN gamma-producing cells express or have expressed IL-4. These results show that effector cells producing either IL-4 or IFN gamma have a common precursor, which expresses the IL-4 gene.