[HTML][HTML] Cytotoxicity of CD56bright NK Cells towards Autologous Activated CD4+ T Cells Is Mediated through NKG2D, LFA-1 and TRAIL and Dampened via CD94 …

N Nielsen, N Ødum, B Ursø, LL Lanier, P Spee - PloS one, 2012 - journals.plos.org
N Nielsen, N Ødum, B Ursø, LL Lanier, P Spee
PloS one, 2012journals.plos.org
In mouse models of chronic inflammatory diseases, Natural Killer (NK) cells can play an
immunoregulatory role by eliminating chronically activated leukocytes. Indirect evidence
suggests that NK cells may also be immunoregulatory in humans. Two subsets of human NK
cells can be phenotypically distinguished as CD16+ CD56dim and CD16dim/− CD56bright.
An expansion in the CD56bright NK cell subset has been associated with clinical responses
to therapy in various autoimmune diseases, suggesting an immunoregulatory role for this …
In mouse models of chronic inflammatory diseases, Natural Killer (NK) cells can play an immunoregulatory role by eliminating chronically activated leukocytes. Indirect evidence suggests that NK cells may also be immunoregulatory in humans. Two subsets of human NK cells can be phenotypically distinguished as CD16+CD56dim and CD16dim/−CD56bright. An expansion in the CD56bright NK cell subset has been associated with clinical responses to therapy in various autoimmune diseases, suggesting an immunoregulatory role for this subset in vivo. Here we compared the regulation of activated human CD4+ T cells by CD56dim and CD56bright autologous NK cells in vitro. Both subsets efficiently killed activated, but not resting, CD4+ T cells. The activating receptor NKG2D, as well as the integrin LFA-1 and the TRAIL pathway, played important roles in this process. Degranulation by NK cells towards activated CD4+ T cells was enhanced by IL-2, IL-15, IL-12+IL-18 and IFN-α. Interestingly, IL-7 and IL-21 stimulated degranulation by CD56bright NK cells but not by CD56dim NK cells. NK cell killing of activated CD4+ T cells was suppressed by HLA-E on CD4+ T cells, as blocking the interaction between HLA-E and the inhibitory CD94/NKG2A NK cell receptor enhanced NK cell degranulation. This study provides new insight into CD56dim and CD56bright NK cell-mediated elimination of activated autologous CD4+ T cells, which potentially may provide an opportunity for therapeutic treatment of chronic inflammation.
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