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Down regulation of human natural killer cell–mediated cytolysis induced by blood transfusion: role of transforming growth factor‐β 1 , soluble Fas ligand, and soluble Class I human leukocyte antigen
Author(s) -
Ghio Massimo,
Contini Paola,
Negrini Simone,
Mazzei Clemente,
Zocchi Maria R.,
Poggi Alessandro
Publication year - 2011
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2010.03000.x
Subject(s) - cytolysis , lymphokine activated killer cell , immunology , nkg2d , natural killer cell , cd16 , k562 cells , immune system , antigen , biology , antibody , interleukin 21 , t cell , in vitro , cytotoxicity , leukemia , cd8 , biochemistry , cd3
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.