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.

Abstract:

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.

journal_name

Transfusion

journal_title

Transfusion

authors

Ghio M,Contini P,Negrini S,Mazzei C,Zocchi MR,Poggi A

doi

10.1111/j.1537-2995.2010.03000.x

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

1567-73

issue

7

eissn

0041-1132

issn

1537-2995

journal_volume

51

pub_type

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