Regulation of the maintenance of peripheral T-cell anergy by TAB1-mediated p38α activation

Kozo Ohkusu-Tsukada, Norio Tominaga, Heiichiro Udono, Katsuyuki Yui

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

In anergic T cells, T-cell receptor (TCR)-mediated responses are functionally inactivated by negative regulatory signals whose mechanisms are poorly understood. Here, we show that CD4+ T cells anergized in vivo by superantigen Mls-1a express a scaffolding protein, transforming growth factor β-activated protein kinase 1-binding protein 1 (TAB1), that negatively regulates TCR signaling through the activation of mitogen-activated protein kinase p38α. TAB1 was not expressed in naive and activated CD4+ T cells. Inhibition of p38 activity in anergic T cells by a chemical inhibitor resulted in the recovery of interleukin 2 (IL-2) and the inhibition of IL-10 secretion. T-cell hybridoma 2B4 cells transduced with TAB1-containing retrovirus (TAB1-2B4 cells) showed activated p38α, inhibited extracellular signal-regulated kinase (ERK) activity, culminating in reduced IL-2 levels and increased IL-10 production. The use of a p38 inhibitor or cotransfection of a dominant-negative form of p38 in TAB1-2B4 cells resulted in the recovery of ERK activity and IL-2 production. These results imply that TAB1-mediated activation of p38α in anergic T cells regulates the maintenance of T-cell unresponsiveness both by inhibiting IL-2 production and by promoting IL-10 production.

Original languageEnglish
Pages (from-to)6957-6966
Number of pages10
JournalMolecular and Cellular Biology
Volume24
Issue number16
DOIs
Publication statusPublished - Aug 2004
Externally publishedYes

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Maintenance
T-Lymphocytes
Interleukin-2
Interleukin-10
T-Cell Antigen Receptor
Superantigens
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
Hybridomas
Transforming Growth Factors
p38 Mitogen-Activated Protein Kinases
Retroviridae
Protein Kinases
Carrier Proteins
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Regulation of the maintenance of peripheral T-cell anergy by TAB1-mediated p38α activation. / Ohkusu-Tsukada, Kozo; Tominaga, Norio; Udono, Heiichiro; Yui, Katsuyuki.

In: Molecular and Cellular Biology, Vol. 24, No. 16, 08.2004, p. 6957-6966.

Research output: Contribution to journalArticle

Ohkusu-Tsukada, Kozo ; Tominaga, Norio ; Udono, Heiichiro ; Yui, Katsuyuki. / Regulation of the maintenance of peripheral T-cell anergy by TAB1-mediated p38α activation. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 16. pp. 6957-6966.
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