title: Enhanced signaling through the IL-2 receptor in CD8+ T cells regulated by antigen recognition results in preferential proliferation and expansion of responding CD8+ T cells rather than promotion of cell death.
abstract: Multiple cytokines, including IL-2, can affect T cell proliferation and survival. However, IL-2 can lead to apoptosis as well as proliferation, making unclear whether IL-2 receptor (IL-2R) signals ultimately have a predominantly positive or negative effect. To address this issue, we examined the effect of enhancing IL-2R signals in CD8(+) T cells after antigen stimulation by engineering a transgenic (Tg) mouse strain with CD8(+) T cells capable of augmented, regulated, autocrine IL-2R signaling after target recognition by means of expression of a chimeric granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-2R. The Tg CD8(+) T cells can bind the granulocyte-macrophage colony-stimulating GM-CSF produced by antigen stimulation, but the GM-CSF binding results in delivery of an IL-2R signal. After antigen stimulation in vivo, the Tg T cells demonstrated marked increases in the initial proliferative response and cell expansion and displayed continued increases in cell expansion after repeated antigen exposure. These data suggest that the predominant role of IL-2R signals delivered to responding CD8(+) T cells is to set the size of the initial response to antigen by promoting T cell proliferation and survival and not cell death.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Laurence E
authors.initials: LE
authors.lastname: Cheng
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlén
authors.forename: Brad H
authors.initials: BH
authors.lastname: Nelson
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
chemical_list: D018398:Homeodomain Proteins; D015375:Receptors, Interleukin-2; C064658:RAG-1 protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor