Journal article
Pretreatment of activated human CD8 T cells with IL-12 leads to enhanced TCR-induced signaling and cytokine production
Molecular immunology, Vol.81, pp.1-15
01/2017
DOI: 10.1016/j.molimm.2016.11.008
PMCID: PMC5201458
PMID: 27883938
Abstract
•Prior exposure to IL-12 enhances TCR-induced cytokine release in human CD8 T cells.•IL-12 pretreatment increases the TCR-induced activation of select signaling pathways.•Primed human CD8 T cells are regulated by IL-12 via an unappreciated mechanism.
During the immune response to pathogens and autoantigens, CD8T cells are exposed to numerous inflammatory agents including the cytokine IL-12. Previous studies have focused on how IL-12 regulates T cell functions when present during or after the activation of the T cell receptor (TCR). However, recent studies suggest that prior exposure to IL-12 also alters the TCR responsiveness of murine T cells. Whether similar phenomena occur in human activated CD8T cells and the mechanisms mediating these effects remain unexplored. In this study, we observed that pretreatment of human activated CD8T cells with IL-12 results in increased cytokine mRNA and protein production following subsequent TCR challenge. The potentiation of TCR-mediated cytokine release was transient and required low doses of IL-12 for at least 24h. Mechanistically, prior exposure to IL-12 increased the TCR induced activation of select MAPKs and AKT without altering the activation of more proximal TCR signaling molecules, suggesting that the IL-12 mediated changes in TCR signaling are responsible for the increased production of cytokines. Our data suggest that prior treatment with IL-12 potentiates human CD8T cell responses at sites of infection and inflammation, expanding our understanding of the function of this clinically important cytokine.
Details
- Title: Subtitle
- Pretreatment of activated human CD8 T cells with IL-12 leads to enhanced TCR-induced signaling and cytokine production
- Creators
- Aldo Vacaflores - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United StatesSamantha N Freedman - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United StatesNicole M Chapman - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United StatesJon C.D Houtman - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Molecular immunology, Vol.81, pp.1-15
- DOI
- 10.1016/j.molimm.2016.11.008
- PMID
- 27883938
- PMCID
- PMC5201458
- NLM abbreviation
- Mol Immunol
- ISSN
- 0161-5890
- eISSN
- 1872-9142
- Publisher
- Elsevier Ltd
- Grant note
- name: National Cancer Institute at the National Institutes of Health, award: CA136729; name: American Heart Association Predoctoral, award: 11PRE7390070; name: NIH Predoctoral Training Grant in Immunology, award: AI007485
- Language
- English
- Date published
- 01/2017
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984094337602771
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