Constitutive expression of a chimeric receptor that delivers IL-2/IL-15 signals allows antigen-independent proliferation of CD8+CD44high but not other T cells

We have prepared transgenic mice whose T cells constitutively express a chimeric receptor combining extracellular human IL-4R and intracellular IL-2R beta segments. This receptor can transmit IL-2/IL-15-like signals in response to human, but not mouse, IL-4, We used these animals to explore to what extent functional IL-2R/IL-15R expression controls the capacity of T cells to proliferate in response to IL-2/IL-15-like signals. After activation with Con A, naive transgenic CD8(+) and CD4(+) T cells respond to human IL-4 as well as to IL-2. Without prior activation, they failed to proliferate in response to human IL-4, although human IL-4 did prolong their survival. Thus, IL-2-induced proliferation of activated T cells requires at least one other Ag-induced change apart from the induction of a functional IL-2R, However, a fraction of CD8(+)CD44(high) T cells proliferate in human IL-4 without antigenic stimulation or syngeneic feeder cells. In contrast, CD4(+)CD44(high) T cells are not constitutively responsive to human IL-4, We conclude that although all transgenic T cells express a functional chimeric receptor, only some CD8(+)CD44(high) T cells contain all molecules required for entry into the cell cycle in response to human IL-4 or IL-15.