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-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.
Gasser
S
S
Lymphocyte Biology Unit, Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland.
Corthésy
P
P
Beerman
F
F
MacDonald
H R
HR
Nabholz
M
M
D000818:Animals; D000941:Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D019409:Interleukin-15 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D016827:CD8 Antigens; D018960:Hyaluronan Receptors; D019409:Interleukin-15; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins; D003208:Concanavalin A; D015847:Interleukin-4