Background: Human Natural Killer (NK) cells are thought to play a role in anti-viral response and tumour immuno-surveillance. The molecular mechanisms of down-regulation of NK cell activity observed after red blood cell transfusion remains unknown. We have found that red cell transfusion could affect NK activity in vivo.Indeed,NK cells isolated from transfused patients did not lyse NK-sensitive target cells but reacquired this property from day 5 to 7 from transfusion.Methods: Thus, we analysed the effect of surnatants,derived from washed red blood cell coats (WRBCC) used in blood transfusion,on NK cell-mediated cytolytic activity.Results: Both autologous and allogeneic WRBCC strongly inhibited the generation of lymphokine activated killer (LAK) cells in a dose dependent manner.Nevertheless,when WRBCC was diluted to 1:100,which represents the actual dilution obtained after blood transfusion in vivo,lysis of NK-resistant target cell Jurkatt was inhibited by 45-63% (n=6). This effect was not due to the down-regulation of triggering molecules as natural cytotoxicity receptors NKp30 or NKp46,CD16,CD244 and NKG2D. The depletion of soluble HLAI (sHLAI) and soluble Fas Ligand (sFasL) from WRBCC,but not of one or another,completely restored the generation of LAK activity.Interestingly, we found that sHLAI,as well as sFasL, induced the rlease of transforming growth factor (TGF-beta) from NK cells and anti-TGF-beta blocking antibodies restored the generation of LAK activity. Conclusions:Altogether,these findings would support the idea that blood transfusion-mediated down-regulation of NK cell activity is linked to sHLAI and sFasL induced production of TGF-beta
Role of soluble HILAI and FasL in the down-regulation of human NK cell-mediated cytolysis induced by blood transfusion
Negrini S;
2007-01-01
Abstract
Background: Human Natural Killer (NK) cells are thought to play a role in anti-viral response and tumour immuno-surveillance. The molecular mechanisms of down-regulation of NK cell activity observed after red blood cell transfusion remains unknown. We have found that red cell transfusion could affect NK activity in vivo.Indeed,NK cells isolated from transfused patients did not lyse NK-sensitive target cells but reacquired this property from day 5 to 7 from transfusion.Methods: Thus, we analysed the effect of surnatants,derived from washed red blood cell coats (WRBCC) used in blood transfusion,on NK cell-mediated cytolytic activity.Results: Both autologous and allogeneic WRBCC strongly inhibited the generation of lymphokine activated killer (LAK) cells in a dose dependent manner.Nevertheless,when WRBCC was diluted to 1:100,which represents the actual dilution obtained after blood transfusion in vivo,lysis of NK-resistant target cell Jurkatt was inhibited by 45-63% (n=6). This effect was not due to the down-regulation of triggering molecules as natural cytotoxicity receptors NKp30 or NKp46,CD16,CD244 and NKG2D. The depletion of soluble HLAI (sHLAI) and soluble Fas Ligand (sFasL) from WRBCC,but not of one or another,completely restored the generation of LAK activity.Interestingly, we found that sHLAI,as well as sFasL, induced the rlease of transforming growth factor (TGF-beta) from NK cells and anti-TGF-beta blocking antibodies restored the generation of LAK activity. Conclusions:Altogether,these findings would support the idea that blood transfusion-mediated down-regulation of NK cell activity is linked to sHLAI and sFasL induced production of TGF-beta
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