The critical role of protein kinase C-θ in Fas/Fas ligand-mediated apoptosis

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Abstract

A functional immune system not only requires rapid expansion of antigenic specific T cells, bat also requires efficient deletion of clonally expanded T cells to avoid accumulation of T cells. Fas/Fas ligand (FasL)-inediated apoptosis plays a critical role in the deletion of activated peripheral T cells, which is clearly demonstrated by superantigen-indiiced expansion and subsequent deletion of T cells. In this study, we show that in the absence of protein kinase C-θ (PKC-θ), superantigen (staphylococcal enterotoxin B)-induced deletion of Vβ8+ CD4+ T cells was defective in PKC-θ-/- mice. In response to staphylococcal enterotoxin B challenge, up-regulation of FasL, but not Fas, was significantly reduced in PKC-θ-/- mice. PKC-θ-/- is thus required for maximum up-regulation of FasL in vivo. We further show that stimulation of FasL expression depends on PKC-θ-mediated activation of NF-AT pathway. In addition, PKC-θ-/- T cells displayed resistance to Fas-mediated apoptosis as well as activation-induced cell death (AICD). In the absence of PKC-θ, Fas-induced activation of apoptotic molecules such as caspase-8, caspase-3, and Bid was not efficient. However, AICD as well as Fas-mediated apoptosis of PKC-θ-/- T cells were restored in the presence of high concentration of IL-2, a critical factor required for potentiating T cells for AICD. PKC-θ is thus required for promoting FasL expression and for potentiating Fas-mediated apoptosis.

Original languageEnglish (US)
Pages (from-to)312-319
Number of pages8
JournalJournal of Immunology
Volume178
Issue number1
StatePublished - Jan 1 2007
Externally publishedYes

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Fas Ligand Protein
Protein Kinase C
Apoptosis
T-Lymphocytes
Superantigens
Cell Death
Up-Regulation
Caspase 8
Caspase 3
Interleukin-2
Immune System

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The critical role of protein kinase C-θ in Fas/Fas ligand-mediated apoptosis. / Manicassamy, Santhakumar; Sun, Zuoming.

In: Journal of Immunology, Vol. 178, No. 1, 01.01.2007, p. 312-319.

Research output: Contribution to journalArticle

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abstract = "A functional immune system not only requires rapid expansion of antigenic specific T cells, bat also requires efficient deletion of clonally expanded T cells to avoid accumulation of T cells. Fas/Fas ligand (FasL)-inediated apoptosis plays a critical role in the deletion of activated peripheral T cells, which is clearly demonstrated by superantigen-indiiced expansion and subsequent deletion of T cells. In this study, we show that in the absence of protein kinase C-θ (PKC-θ), superantigen (staphylococcal enterotoxin B)-induced deletion of Vβ8+ CD4+ T cells was defective in PKC-θ-/- mice. In response to staphylococcal enterotoxin B challenge, up-regulation of FasL, but not Fas, was significantly reduced in PKC-θ-/- mice. PKC-θ-/- is thus required for maximum up-regulation of FasL in vivo. We further show that stimulation of FasL expression depends on PKC-θ-mediated activation of NF-AT pathway. In addition, PKC-θ-/- T cells displayed resistance to Fas-mediated apoptosis as well as activation-induced cell death (AICD). In the absence of PKC-θ, Fas-induced activation of apoptotic molecules such as caspase-8, caspase-3, and Bid was not efficient. However, AICD as well as Fas-mediated apoptosis of PKC-θ-/- T cells were restored in the presence of high concentration of IL-2, a critical factor required for potentiating T cells for AICD. PKC-θ is thus required for promoting FasL expression and for potentiating Fas-mediated apoptosis.",
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N2 - A functional immune system not only requires rapid expansion of antigenic specific T cells, bat also requires efficient deletion of clonally expanded T cells to avoid accumulation of T cells. Fas/Fas ligand (FasL)-inediated apoptosis plays a critical role in the deletion of activated peripheral T cells, which is clearly demonstrated by superantigen-indiiced expansion and subsequent deletion of T cells. In this study, we show that in the absence of protein kinase C-θ (PKC-θ), superantigen (staphylococcal enterotoxin B)-induced deletion of Vβ8+ CD4+ T cells was defective in PKC-θ-/- mice. In response to staphylococcal enterotoxin B challenge, up-regulation of FasL, but not Fas, was significantly reduced in PKC-θ-/- mice. PKC-θ-/- is thus required for maximum up-regulation of FasL in vivo. We further show that stimulation of FasL expression depends on PKC-θ-mediated activation of NF-AT pathway. In addition, PKC-θ-/- T cells displayed resistance to Fas-mediated apoptosis as well as activation-induced cell death (AICD). In the absence of PKC-θ, Fas-induced activation of apoptotic molecules such as caspase-8, caspase-3, and Bid was not efficient. However, AICD as well as Fas-mediated apoptosis of PKC-θ-/- T cells were restored in the presence of high concentration of IL-2, a critical factor required for potentiating T cells for AICD. PKC-θ is thus required for promoting FasL expression and for potentiating Fas-mediated apoptosis.

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