TRAF3 regulates homeostasis of CD8+ central memory T cells

Zuoan Yi; Laura L Stunz; Wai Wai Lin; Gail A Bishop

doi:10.1371/journal.pone.0102120

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TRAF3 regulates homeostasis of CD8+ central memory T cells

Journal article

Open access

Peer reviewed

TRAF3 regulates homeostasis of CD8+ central memory T cells

Zuoan Yi, Laura L Stunz, Wai Wai Lin and Gail A Bishop

PloS one, Vol.9(7), pp.e102120-e102120

2014

DOI: 10.1371/journal.pone.0102120

PMCID: PMC4092107

PMID: 25010048

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Abstract

Our laboratory reported previously that TNF receptor associated factor 3 (TRAF3) is a positive regulator of TCR signaling and T cell function. In the current study, we present new findings that reveal differential roles for TRAF3 in the regulation of CD4+ and CD8(+) T cells. In response to TCR stimulation in vitro, TRAF3 has greater impact in CD4(+) T cells than in CD8+ T cells. However, T cell-specific TRAF3 deficient mice (CD4Cre TRAF3(fl°x)/(fl°x); T-TRAF3(-/-)) have a greater number of CD4(+)CD44(hi) effector/memory T cells than littermate control (LMC) mice, possibly due to an inefficient suppressive effect of TRAF3 deficient Foxp3+ regulatory T cells. In contrast, CD8(+)CD44(hi)CD62L(hi) central memory (Tcm) cells are markedly reduced in T-TRAF3(-/-) mice in comparison to LMC mice, although CD8(+)CD44(hi)CD62L(l°w) effector memory T (Tem) cells and naïve T cells (CD8(+)CD44(l°w)CD62L(hi)) do not show significant differences in number. Importantly, TRAF3-deficient Tcm cells exhibit defective homeostasis due to impaired IL-15 signaling. These results indicate that the involvement of TRAF3 in IL-15 mediated signaling to T cells plays a previously unappreciated and critical role in CD8(+) Tcm cell regulation and maintenance.

TNF Receptor-Associated Factor 3 - deficiency

Receptors, Antigen, T-Cell - metabolism

Signal Transduction

Mice, Inbred C57BL

Homeostasis - immunology

Male

TNF Receptor-Associated Factor 3 - metabolism

CD4-Positive T-Lymphocytes - immunology

Lymphocyte Activation - immunology

Animals

Interleukin-15 - metabolism

Female

Immunologic Memory

CD8-Positive T-Lymphocytes - immunology

Details

Title: Subtitle: TRAF3 regulates homeostasis of CD8+ central memory T cells
Creators: Zuoan Yi - Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America
Laura L Stunz - Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America
Wai Wai Lin - Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America; Graduate Immunology Program, University of Iowa, Iowa City, Iowa, United States of America
Gail A Bishop - Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America; Graduate Immunology Program, University of Iowa, Iowa City, Iowa, United States of America; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America; VA Medical Center, Iowa City, Iowa, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.9(7), pp.e102120-e102120
DOI: 10.1371/journal.pone.0102120
PMID: 25010048
PMCID: PMC4092107
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS AI28847 / NIAID NIH HHS I01 BX001702 / BLRD VA T32 AI007260 / NIAID NIH HHS P30CA086862 / NCI NIH HHS
Language: English
Date published: 2014
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001161802771

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