BACKGROUND: Human natural killer (NK) cells are thought to play a role in antiviral response and tumor immune surveillance. The molecular mechanisms of down regulation of NK-cell activity observed after red blood cell (RBC) transfusion is still undefined. STUDY DESIGN AND METHODS: Both effects of blood transfusion (ex vivo) and supernatants (SNs) derived from RBC units unstored (RBC-0) or stored for 5 or 30 days (RBC-5 or -30, respectively) in vitro were analyzed on NK cell-mediated cytolytic activity. RESULTS: We have found that NK cells isolated from transfused patients on Day 3 lysed the NK-sensitive target cells K562 to a lesser extent than before transfusion. This down regulation of NK-cell activation was evident also for NK-cell killing mediated through the engagement of NK cell-activating receptors as NKG2D, NKp30, NKp46, and CD16. Transfused patients reacquired NK cell-mediated cytolytic activity from Day 5 to Day 7 after transfusion. SN from RBC-30, but not from RBC-0 or RBC-5, strongly inhibited the generation of lymphokine-activated killer (LAK) cells and lysis of the NK-resistant target cell Jurkat in a dose-dependent manner. Transforming growth factor-β1 (TGF-β1) blocking antibodies partially restored the generation of LAK activity. In addition, the depletion of both soluble Class I human leukocyte antigens (sHLA-I) and soluble Fas ligand (sFasL) from SN of RBC-30 completely 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 mediated by sHLA-I, sFasL, and TGF-β1.
BACKGROUND:Human natural killer (NK) cells are thought to play a role in antiviral response and tumor immune surveillance. The molecular mechanisms of down regulation of NK-cell activity observed after red blood cell (RBC) transfusion is still undefined. STUDY DESIGN AND METHODS: Both effects of blood transfusion (ex vivo) and supernatants (SNs) derived from RBC units unstored (RBC-0) or stored for 5 or 30 days (RBC-5 or -30, respectively) in vitro were analyzed on NK cell-mediated cytolytic activity. RESULTS: We have found that NK cells isolated from transfused patients on Day 3 lysed the NK-sensitive target cells K562 to a lesser extent than before transfusion. This down regulation of NK-cell activation was evident also for NK-cell killing mediated through the engagement of NK cell-activating receptors as NKG2D, NKp30, NKp46, and CD16. Transfused patients reacquired NK cell-mediated cytolytic activity from Day 5 to Day 7 after transfusion. SN from RBC-30, but not from RBC-0 or RBC-5, strongly inhibited the generation of lymphokine-activated killer (LAK) cells and lysis of the NK-resistant target cell Jurkat in a dose-dependent manner. Transforming growth factor-β1 (TGF-β1) blocking antibodies partially restored the generation of LAK activity. In addition, the depletion of both soluble Class I human leukocyte antigens (sHLA-I) and soluble Fas ligand (sFasL) from SN of RBC-30 completely 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 mediated by sHLA-I, sFasL, and TGF-β1.
Authors: Annemiek M Dekker; Jimme K Wiggers; Robert J Coelen; Rowan F van Golen; Marc G H Besselink; Olivier R C Busch; Joanne Verheij; Markus W Hollmann; Thomas M van Gulik Journal: HPB (Oxford) Date: 2016-01-06 Impact factor: 3.647
Authors: Kenneth E Remy; Mark W Hall; Jill Cholette; Nicole P Juffermans; Kathleen Nicol; Allan Doctor; Neil Blumberg; Philip C Spinella; Philip J Norris; Mary K Dahmer; Jennifer A Muszynski Journal: Transfusion Date: 2018-01-30 Impact factor: 3.157
Authors: Jennifer A Muszynski; Philip C Spinella; Jill M Cholette; Jason P Acker; Mark W Hall; Nicole P Juffermans; Daniel P Kelly; Neil Blumberg; Kathleen Nicol; Jennifer Liedel; Allan Doctor; Kenneth E Remy; Marisa Tucci; Jacques Lacroix; Philip J Norris Journal: Transfusion Date: 2016-10-02 Impact factor: 3.157