RKIP contributes to IFN-γ synthesis by CD8+ T cells after serial TCR triggering in systemic inflammatory response syndrome.
نویسندگان
چکیده
Systemic inflammatory response syndrome (SIRS) is associated with the development of severe medical complications, including progression to multiple organ dysfunction syndrome and even death. To date, only marginal improvements in terms of therapeutic options have been established for patients affected by SIRS. Raf kinase inhibitor protein (RKIP) is a regulator of MAPK and NF-κB signaling cascades, which are both critical for production of the proinflammatory cytokines responsible for SIRS initiation. By testing a T cell-dependent mouse model of SIRS that utilizes staphylococcal enterotoxin A specific for Vβ3(+) T cells, we show that RKIP is necessary for the exaggerated production of IFN-γ from SIRS splenocytes. This effect was not due to differences in T cell expansion, IL-10 production, or APC priming, but rather a cell-intrinsic defect lying downstream of the TCR in staphylococcal enterotoxin A-specific CD8(+) T cells. Importantly, mice lacking RKIP were still able to proliferate, survive, and contribute to cytokine production in response to pathogen associated molecular pattern-TLR-mediated stimuli, despite the TCR-dependent defects seen in our SIRS model. Finally, by blocking RKIP in wild-type SIRS splenocytes, the IFN-γ response by CD8(+) Vβ3(+) T cells was significantly diminished. These data suggest that RKIP may be a potential therapeutic target in SIRS by curbing effector cytokine production from CD8(+) T cells during serial TCR triggering.
منابع مشابه
RKIP Contributes to IFN-g Synthesis by CD8 T Cells after Serial TCR Triggering in Systemic Inflammatory Response Syndrome
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عنوان ژورنال:
- Journal of immunology
دوره 191 2 شماره
صفحات -
تاریخ انتشار 2013