Article: article from journal or magazin.
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.
Journal of Immunology
We have prepared transgenic mice whose T cells constitutively express a chimeric receptor combining extracellular human IL-4R and intracellular IL-2Rbeta 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+CD44high T cells proliferate in human IL-4 without antigenic stimulation or syngeneic feeder cells. In contrast, CD4+CD44high 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+CD44high T cells contain all molecules required for entry into the cell cycle in response to human IL-4 or IL-15.
Animals, Antigens/immunology, Antigens, CD44/biosynthesis, Antigens, CD8/biosynthesis, CD8-Positive T-Lymphocytes/immunology, Cells, Cultured, Concanavalin A/immunology, Humans, Interleukin-15/physiology, Interleukin-4/physiology, Lymphocyte Activation/genetics, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Inbred DBA, Mice, Transgenic, Protein Binding/genetics, Protein Binding/immunology, Receptors, Interleukin-2/biosynthesis, Receptors, Interleukin-2/genetics, Receptors, Interleukin-4/biosynthesis, Receptors, Interleukin-4/genetics, Recombinant Fusion Proteins/biosynthesis, Recombinant Fusion Proteins/physiology, Signal Transduction/genetics, Signal Transduction/immunology, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/metabolism
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