Journal article
IL-12 and type I interferon prolong the division of activated CD8 T cells by maintaining high-affinity IL-2 signaling in vivo
The Journal of experimental medicine, Vol.211(1), pp.105-120
01/13/2014
DOI: 10.1084/jem.20130901
PMCID: PMC3892973
PMID: 24367005
Abstract
TCR ligation and co-stimulation induce cellular division; however, optimal accumulation of effector CD8 T cells requires direct inflammatory signaling by signal 3 cytokines, such as IL-12 or type I IFNs. Although in vitro studies suggest that IL-12/type I IFN may enhance T cell survival or early proliferation, the mechanisms underlying optimal accumulation of CD8 T cells in vivo are unknown. In particular, it is unclear if disparate signal 3 cytokines optimize effector CD8 T cell accumulation by the same mechanism and how these inflammatory cytokines, which are transiently produced early after infection, affect T cell accumulation many days later at the peak of the immune response. Here, we show that transient exposure of CD8 T cells to IL-12 or type I IFN does not promote survival or confer an early proliferative advantage in vivo, but rather sustains surface expression of CD25, the high-affinity IL-2 receptor. This prolongs division of CD8 T cells in response to basal IL-2, through activation of the PI3K pathway and expression of FoxM1, a positive regulator of cell cycle progression genes. Thus, signal 3 cytokines use a common pathway to optimize effector CD8 T cell accumulation through a temporally orchestrated sequence of cytokine signals that sustain division rather than survival.
Details
- Title: Subtitle
- IL-12 and type I interferon prolong the division of activated CD8 T cells by maintaining high-affinity IL-2 signaling in vivo
- Creators
- Gabriel R Starbeck-Miller - Interdisciplinary Graduate Program in Immunology, Department of Microbiology, and Department of Pathology, University of Iowa, Iowa City, IA 52242Hai-Hui Xue - Interdisciplinary Graduate Program in Immunology, Department of Microbiology, and Department of Pathology, University of Iowa, Iowa City, IA 52242, Interdisciplinary Graduate Program in Immunology, Department of Microbiology, and Department of Pathology, University of Iowa, Iowa City, IA 52242John T Harty - Interdisciplinary Graduate Program in Immunology, Department of Microbiology, and Department of Pathology, University of Iowa, Iowa City, IA 52242, Interdisciplinary Graduate Program in Immunology, Department of Microbiology, and Department of Pathology, University of Iowa, Iowa City, IA 52242, Interdisciplinary Graduate Program in Immunology, Department of Microbiology, and Department of Pathology, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.211(1), pp.105-120
- DOI
- 10.1084/jem.20130901
- PMID
- 24367005
- PMCID
- PMC3892973
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 01/13/2014
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984046908602771
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