TY - JOUR
T1 - The critical role of protein kinase C-θ in Fas/Fas ligand-mediated apoptosis
AU - Manicassamy, Santhakumar
AU - Sun, Zuoming
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2007/1/1
Y1 - 2007/1/1
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.
AB - 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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U2 - 10.4049/jimmunol.178.1.312
DO - 10.4049/jimmunol.178.1.312
M3 - Article
C2 - 17182568
AN - SCOPUS:33845921462
SN - 0022-1767
VL - 178
SP - 312
EP - 319
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -