IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism

Jian Zhang; Tamás Bárdos; Qing Shao; Jurg Tschopp; Katalin Mikecz; Tibor T Glant; Alison Finnegan

doi:10.4049/jimmunol.170.7.3495

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IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism

Journal article

Peer reviewed

IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism

Jian Zhang, Tamás Bárdos, Qing Shao, Jurg Tschopp, Katalin Mikecz, Tibor T Glant and Alison Finnegan

The Journal of immunology (1950), Vol.170(7), pp.3495-3503

04/01/2003

DOI: 10.4049/jimmunol.170.7.3495

PMID: 12646610

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Abstract

Activation-induced cell death (AICD) of T cells is one of the major mechanisms of peripheral tolerance. The regulation of AICD by IL-4 is poorly understood. In this study, we report that AICD in IL-4-deficient T cells is significantly reduced compared with that in wild-type T cells. This impaired AICD correlates with the failure to induce degradation of cellular FLIP. IL-4-mediated enhancement of AICD and cellular FLIP degradation requires a Janus kinase/STAT-6 signaling pathway. Unexpectedly, these effects of IL-4 could be blocked by a neutralizing anti-IL-2 Ab, and addition of rIL-2 could completely restore the defective AICD in IL-4-deficient T cells. Furthermore, IL-4 regulates the T cell thresholds for IL-2 signaling during AICD. These data suggest that IL-4 promotes AICD via an IL-2-dependent mechanism.

T-Lymphocyte Subsets - immunology

T-Lymphocyte Subsets - cytology

Membrane Glycoproteins - biosynthesis

Apoptosis - genetics

fas Receptor - metabolism

STAT6 Transcription Factor

Trans-Activators - physiology

Signal Transduction - immunology

Interleukin-2 - physiology

Lymphocyte Activation - genetics

Trans-Activators - genetics

Adjuvants, Immunologic - genetics

Interleukin-4 - genetics

Interleukin-4 - physiology

Adjuvants, Immunologic - deficiency

Adjuvants, Immunologic - physiology

Mice, Inbred C57BL

Cells, Cultured

Intracellular Signaling Peptides and Proteins

Interleukin-4 - deficiency

Mice, Transgenic

Proto-Oncogene Proteins c-bcl-2 - biosynthesis

Receptors, Antigen, T-Cell - physiology

Mice, Knockout

Drug Synergism

Fas Ligand Protein

Animals

Apoptosis - immunology

Carrier Proteins - metabolism

Trans-Activators - deficiency

Up-Regulation - immunology

T-Lymphocyte Subsets - metabolism

Ligands

CASP8 and FADD-Like Apoptosis Regulating Protein

Mice

Mice, Inbred BALB C

Details

Title: Subtitle: IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism
Creators: Jian Zhang - Section of Biochemistry and Molecular Biology, Department of Orthopedic Surgery, Rush University at Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. jzhang1@rush.edu
Tamás Bárdos
Qing Shao
Jurg Tschopp
Katalin Mikecz
Tibor T Glant
Alison Finnegan
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.170(7), pp.3495-3503
DOI: 10.4049/jimmunol.170.7.3495
PMID: 12646610
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AR49047 / NIAMS NIH HHS AR45652 / NIAMS NIH HHS AR47412 / NIAMS NIH HHS AR40310 / NIAMS NIH HHS
Language: English
Date published: 04/01/2003
Academic Unit: Pathology
Record Identifier: 9984047643702771

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