Differential effects of IL-12 on Tregs and non-Treg T cells: roles of IFN-γ, IL-2 and IL-2R

Jingxian Zhao; Jincun Zhao; Stanley Perlman

doi:10.1371/journal.pone.0046241

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Differential effects of IL-12 on Tregs and non-Treg T cells: roles of IFN-γ, IL-2 and IL-2R

Journal article

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Peer reviewed

Differential effects of IL-12 on Tregs and non-Treg T cells: roles of IFN-γ, IL-2 and IL-2R

Jingxian Zhao, Jincun Zhao and Stanley Perlman

PloS one, Vol.7(9), pp.e46241-e46241

2012

DOI: 10.1371/journal.pone.0046241

PMCID: PMC3459844

PMID: 23029447

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Abstract

Complex interactions between effector T cells and Foxp3(+) regulatory T cells (Treg) contribute to clinical outcomes in cancer, and autoimmune and infectious diseases. Previous work showed that IL-12 reversed Treg-mediated suppression of CD4(+)Foxp3(-) T cell (Tconv) proliferation. We and others have also shown that Tregs express T-bet and IFN-γ at sites of Th1 inflammation and that IL-12 induces IFN-γ production by Tregs in vitro. To investigate whether loss of immunosuppression occurs when IFN-γ is expressed by Tregs we treated mouse lymphocyte cultures with IL-12. IFN-γ expression did not decrease the ability of Tregs to suppress Tconv proliferation. Rather, IL-12 treatment decreased Treg frequency and Foxp3 levels in Tregs. We further showed that IL-12 increased IL-2R expression on Tconv and CD8 T cells, diminished its expression on Tregs and decreased IL-2 production by Tconv and CD8 T cells. Together, these IL-12 mediated changes favored the outgrowth of non-Tregs. Additionally, we showed that treatment with a second cytokine, IL-27, decreased IL-2 expression without augmenting Tconv and CD8 T cell proliferation. Notably, IL-27 only slightly modified levels of IL-2R on non-Treg T cells. Together, these results show that IL-12 has multiple effects that modify the balance between Tregs and non-Tregs and support an important role for relative levels of IL-2R but not for IFN-γ expression in IL-12-mediated reversal of Treg immunosuppression.

Forkhead Transcription Factors - immunology

CD8-Positive T-Lymphocytes - cytology

Gene Expression - drug effects

Humans

T-Box Domain Proteins - immunology

T-Lymphocytes, Regulatory - immunology

Receptors, Interleukin-2 - genetics

T-Lymphocytes, Helper-Inducer - drug effects

Interleukin-2 - immunology

T-Lymphocytes, Helper-Inducer - immunology

Gene Expression - immunology

T-Lymphocytes, Helper-Inducer - cytology

T-Lymphocytes, Regulatory - cytology

Interferon-gamma - genetics

Interleukins - pharmacology

CD4 Antigens - genetics

Interleukin-12 - pharmacology

CD4 Antigens - immunology

Cells, Cultured

Forkhead Transcription Factors - genetics

Organ Specificity

Receptors, Interleukin-2 - immunology

T-Box Domain Proteins - genetics

Interleukin-2 - genetics

T-Lymphocytes, Regulatory - drug effects

Animals

CD8-Positive T-Lymphocytes - drug effects

Interferon-gamma - immunology

Mice

CD8-Positive T-Lymphocytes - immunology

Details

Title: Subtitle: Differential effects of IL-12 on Tregs and non-Treg T cells: roles of IFN-γ, IL-2 and IL-2R
Creators: Jingxian Zhao - Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America
Jincun Zhao
Stanley Perlman
Resource Type: Journal article
Publication Details: PloS one, Vol.7(9), pp.e46241-e46241
DOI: 10.1371/journal.pone.0046241
PMID: 23029447
PMCID: PMC3459844
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: R01 NS36592 / NINDS NIH HHS R01 NS036592 / NINDS NIH HHS
Language: English
Date published: 2012
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777475802771

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