Down regulation of human natural killer cell-mediated cytolysis induced by blood transfusion: Role of transforming growth factor-β1, soluble Fas ligand, and soluble Class i human leukocyte antigen

Massimo Ghio, Paola Contini, Simone Negrini, Clemente Mazzei, Maria R. Zocchi, Alessandro Poggi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1567-1573
Number of pages7
JournalTransfusion
Volume51
Issue number7
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Fas Ligand Protein
Transforming Growth Factors
HLA Antigens
Blood Transfusion
Natural Killer Cells
Down-Regulation
Erythrocytes
Lymphokines
Natural Killer Cell Receptors
Lymphokine-Activated Killer Cells
Erythrocyte Transfusion
Blocking Antibodies
Jurkat Cells
K562 Cells
Antiviral Agents

ASJC Scopus subject areas

  • Hematology
  • Immunology
  • Immunology and Allergy

Cite this

Down regulation of human natural killer cell-mediated cytolysis induced by blood transfusion : Role of transforming growth factor-β1, soluble Fas ligand, and soluble Class i human leukocyte antigen. / Ghio, Massimo; Contini, Paola; Negrini, Simone; Mazzei, Clemente; Zocchi, Maria R.; Poggi, Alessandro.

In: Transfusion, Vol. 51, No. 7, 07.2011, p. 1567-1573.

Research output: Contribution to journalArticle

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AB - 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.

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