Exposure of Human CD4 T Cells to IL-12 Results in Enhanced TCR-Induced Cytokine Production, Altered TCR Signaling, and Increased Oxidative Metabolism

Aldo Vacaflores; Nicole M Chapman; John T Harty; Martin J Richer; Jon C D Houtman

doi:10.1371/journal.pone.0157175

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Exposure of Human CD4 T Cells to IL-12 Results in Enhanced TCR-Induced Cytokine Production, Altered TCR Signaling, and Increased Oxidative Metabolism

Journal article

Open access

Peer reviewed

Exposure of Human CD4 T Cells to IL-12 Results in Enhanced TCR-Induced Cytokine Production, Altered TCR Signaling, and Increased Oxidative Metabolism

Aldo Vacaflores, Nicole M Chapman, John T Harty, Martin J Richer and Jon C D Houtman

PloS one, Vol.11(6), e0157175

2016

DOI: 10.1371/journal.pone.0157175

PMCID: PMC4900534

PMID: 27280403

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Abstract

Human CD4 T cells are constantly exposed to IL-12 during infections and certain autoimmune disorders. The current paradigm is that IL-12 promotes the differentiation of naïve CD4 T cells into Th1 cells, but recent studies suggest IL-12 may play a more complex role in T cell biology. We examined if exposure to IL-12 alters human CD4 T cell responses to subsequent TCR stimulation. We found that IL-12 pretreatment increased TCR-induced IFN-γ, TNF-α, IL-13, IL-4 and IL-10 production. This suggests that prior exposure to IL-12 potentiates the TCR-induced release of a range of cytokines. We observed that IL-12 mediated its effects through both transcriptional and post-transcriptional mechanisms. IL-12 pretreatment increased the phosphorylation of AKT, p38 and LCK following TCR stimulation without altering other TCR signaling molecules, potentially mediating the increase in transcription of cytokines. In addition, the IL-12-mediated enhancement of cytokines that are not transcriptionally regulated was partially driven by increased oxidative metabolism. Our data uncover a novel function of IL-12 in human CD4 T cells; specifically, it enhances the release of a range of cytokines potentially by altering TCR signaling pathways and by enhancing oxidative metabolism.

Transcription, Genetic - drug effects

Humans

Middle Aged

CD4-Positive T-Lymphocytes - metabolism

Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - immunology

Male

p38 Mitogen-Activated Protein Kinases - immunology

Signal Transduction - immunology

Proto-Oncogene Proteins c-akt - immunology

Signal Transduction - drug effects

Adolescent

Oxidation-Reduction - drug effects

Transcription, Genetic - immunology

Adult

Female

Receptors, Antigen, T-Cell - immunology

Phosphorylation - immunology

Phosphorylation - drug effects

Cytokines - immunology

Interleukin-12 - pharmacology

Details

Title: Subtitle: Exposure of Human CD4 T Cells to IL-12 Results in Enhanced TCR-Induced Cytokine Production, Altered TCR Signaling, and Increased Oxidative Metabolism
Creators: Aldo Vacaflores - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America
Nicole M Chapman - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America
John T Harty - Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America
Martin J Richer - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
Jon C D Houtman - Department of Internal Medicine, Division of Immunology, University of Iowa, Iowa City, Iowa, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.11(6), e0157175
DOI: 10.1371/journal.pone.0157175
PMID: 27280403
PMCID: PMC4900534
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R37 AI042767 / NIAID NIH HHS R01 AI095178 / NIAID NIH HHS R01 AI100527 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS R56 AI106776 / NIAID NIH HHS R01 CA136729 / NCI NIH HHS R01 AI042767 / NIAID NIH HHS R01 AI085515 / NIAID NIH HHS R21 AI042767 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 2016
Academic Unit: Microbiology and Immunology; Pathology; Internal Medicine
Record Identifier: 9984047735802771

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