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. 2016 Sep 22;7(9):e2373.
doi: 10.1038/cddis.2016.273.

Oxidative downmodulation of T cell-mediated cytotoxicity

Guido H Wabnitz  1 , Yvonne Samstag  1
Affiliations

Oxidative downmodulation of T cell-mediated cytotoxicity

Guido H Wabnitz et al. Cell Death Dis. .
No abstract available

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Figures

Figure 1
Figure 1
Cellular and molecular regulation of serial killing and its inhibition by WF10. (a) Cellular level. Cytotoxic T cells (CTLs) migrate as solitaire cells during the immune surveillance into inflammed tissues in order to find target cells. After encountering a target cells, CTLs firmly adhere to these cells and induce their apoptosis (first kill, upper row). To kill a second target cell, CTLs need to detach from the dying target cell and attach to a second target cell, perform the second kill and so on. One CTL can kill more than 6 target cells in a row. WF10 interferes with detachment of the CTL from their initial target cell (lower row). This leads to a strong decrease in the killing frequency of CTLs. (b) Molecular level. The attachment/detachment cycle during serial killing is dependent on an LFA-1 avidity up- and down regulation circle (upper row). The molecular motor regulating the LFA-1 avidity is the actin bundling protein L-plastin (LPL). L-plastin is transiently phosphorylated upon target cell encounter. Only the dephosphorylation of L-plastin enables the downregulation of LFA-1 avidity and the detachment of CTLs from the target cell. WF10 shifts the balance toward phosphorylated L-plastin by an as yet unknown mechanism and, thereby, prevents serial killing (lower row)
See this image and copyright information in PMC

References

    1. Reuter S et al Free Radic Biol Med 2010; 49: 1603–1616. - PMC - PubMed
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    1. Samstag Y et al Immunol Rev 2013; 256: 30–47. - PMC - PubMed
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