TNF receptor-associated factor 3 is required for T cell-mediated immunity and TCR/CD28 signaling

Ping Xie; Zachary J Kraus; Laura L Stunz; Yan Liu; Gail A Bishop

doi:10.4049/jimmunol.1000290

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TNF receptor-associated factor 3 is required for T cell-mediated immunity and TCR/CD28 signaling

Journal article

Peer reviewed

TNF receptor-associated factor 3 is required for T cell-mediated immunity and TCR/CD28 signaling

Ping Xie, Zachary J Kraus, Laura L Stunz, Yan Liu and Gail A Bishop

The Journal of immunology (1950), Vol.186(1), pp.143-155

01/01/2011

DOI: 10.4049/jimmunol.1000290

PMCID: PMC3044490

PMID: 21084666

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Abstract

We recently reported that TNFR-associated factor (TRAF)3, a ubiquitously expressed adaptor protein, promotes mature B cell apoptosis. However, the specific function of TRAF3 in T cells has remained unclear. In this article, we report the generation and characterization of T cell-specific TRAF3(-/-) mice, in which the traf3 gene was deleted from thymocytes and T cells. Ablation of TRAF3 in the T cell lineage did not affect CD4 or CD8 T cell populations in secondary lymphoid organs or the numbers or proportions of CD4(+),CD8(+) or double-positive or double-negative thymocytes, except that the T cell-specific TRAF3(-/-) mice had a 2-fold increase in FoxP3(+) T cells. In striking contrast to mice lacking TRAF3 in B cells, the T cell TRAF3-deficient mice exhibited defective IgG1 responses to a T-dependent Ag, as well as impaired T cell-mediated immunity to infection with Listeria monocytogenes. Surprisingly, we found that TRAF3 was recruited to the TCR/CD28 signaling complex upon costimulation and that TCR/CD28-mediated proximal and distal signaling events were compromised by TRAF3 deficiency. These findings provide insights into the roles played by TRAF3 in T cell activation and T cell-mediated immunity.

TNF Receptor-Associated Factor 3 - physiology

CD4-Positive T-Lymphocytes - immunology

Signal Transduction - immunology

Antibodies, Bacterial - biosynthesis

Immunoglobulin G - biosynthesis

T-Lymphocytes - metabolism

TNF Receptor-Associated Factor 3 - genetics

Listeriosis - immunology

CD8-Positive T-Lymphocytes - metabolism

T-Lymphocytes - pathology

CD28 Antigens - physiology

CD4-Positive T-Lymphocytes - microbiology

CD8-Positive T-Lymphocytes - microbiology

Immunity, Cellular - genetics

TNF Receptor-Associated Factor 3 - deficiency

Listeriosis - genetics

Mice, Inbred C57BL

CD4-Positive T-Lymphocytes - metabolism

Cells, Cultured

Mice, Transgenic

Signal Transduction - genetics

Receptors, Antigen, T-Cell - physiology

Mice, Knockout

Animals

Listeriosis - pathology

T-Lymphocytes - immunology

Mice

CD8-Positive T-Lymphocytes - immunology

Details

Title: Subtitle: TNF receptor-associated factor 3 is required for T cell-mediated immunity and TCR/CD28 signaling
Creators: Ping Xie - Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
Zachary J Kraus
Laura L Stunz
Yan Liu
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.186(1), pp.143-155
DOI: 10.4049/jimmunol.1000290
PMID: 21084666
PMCID: PMC3044490
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: R01 AI028847-19 / NIAID NIH HHS AI28847 / NIAID NIH HHS R01 AI028847 / NIAID NIH HHS P30 CA072720 / NCI NIH HHS R56 AI028847 / NIAID NIH HHS
Language: English
Date published: 01/01/2011
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001217102771

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