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 language | English |
|---|---|
| Pages (from-to) | 1567-1573 |
| Number of pages | 7 |
| Journal | Transfusion |
| Volume | 51 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2011 |
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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 journal › Article
}
TY - JOUR
T1 - Down regulation of human natural killer cell-mediated cytolysis induced by blood transfusion
T2 - Role of transforming growth factor-β1, soluble Fas ligand, and soluble Class i human leukocyte antigen
AU - Ghio, Massimo
AU - Contini, Paola
AU - Negrini, Simone
AU - Mazzei, Clemente
AU - Zocchi, Maria R.
AU - Poggi, Alessandro
PY - 2011/7
Y1 - 2011/7
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=79960184745&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960184745&partnerID=8YFLogxK
U2 - 10.1111/j.1537-2995.2010.03000.x
DO - 10.1111/j.1537-2995.2010.03000.x
M3 - Article
C2 - 21214580
AN - SCOPUS:79960184745
VL - 51
SP - 1567
EP - 1573
JO - Transfusion
JF - Transfusion
SN - 0041-1132
IS - 7
ER -