10.3389/fimmu.2019.00547.s003
Ming Ni
Ming
Ni
Lei Wang
Lei
Wang
Mingya Yang
Mingya
Yang
Brigitte Neuber
Brigitte
Neuber
Leopold Sellner
Leopold
Sellner
Angela Hückelhoven-Krauss
Angela
Hückelhoven-Krauss
Maria-Luisa Schubert
Maria-Luisa
Schubert
Thomas Luft
Thomas
Luft
Ute Hegenbart
Ute
Hegenbart
Stefan Schönland
Stefan
Schönland
Patrick Wuchter
Patrick
Wuchter
Bao-an Chen
Bao-an
Chen
Volker Eckstein
Volker
Eckstein
William Krüger
William
Krüger
Ronit Yerushalmi
Ronit
Yerushalmi
Katia Beider
Katia
Beider
Arnon Nagler
Arnon
Nagler
Carsten Müller-Tidow
Carsten
Müller-Tidow
Peter Dreger
Peter
Dreger
Michael Schmitt
Michael
Schmitt
Anita Schmitt
Anita
Schmitt
Table_1_Shaping of CD56bri Natural Killer Cells in Patients With Steroid-Refractory/Resistant Acute Graft-vs.-Host Disease via Extracorporeal Photopheresis.docx
Frontiers
2019
GvHD
ECP
immunomodulation
natural killer cells
anti-viral effect
anti-leukemia effect
2019-03-20 12:58:23
Dataset
https://frontiersin.figshare.com/articles/dataset/Table_1_Shaping_of_CD56bri_Natural_Killer_Cells_in_Patients_With_Steroid-Refractory_Resistant_Acute_Graft-vs_-Host_Disease_via_Extracorporeal_Photopheresis_docx/7868345
<p>CD56<sup>bri</sup> natural killer (NK) cells play an important role in the pathogenesis of graft-vs. -host disease (GVHD) and immune defense in the early period after allogeneic hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP) as an immunomodulating therapy has been widely used for GVHD treatment. However, the mechanism of action of ECP still remains to be elucidated, particularly the influence of ECP on NK cells. Thirty-four patients with steroid-refractory/resistant acute GVHD (aGVHD) ≥ °II and moderate to severe chronic GVHD (cGVHD) received ECP therapy. Patient samples obtained during intensive and long-term treatment were analyzed. Immunomonitoring with respect to cell phenotype and function was performed on rested peripheral blood mononuclear cells (PBMCs) using multiparametric flow cytometry. NK activity in terms of cytokine release was analyzed by intracellular cytokine staining after co-culture with K562 cells. Moreover, the proliferative capacity of NK cells, CD4<sup>+</sup>, and CD8<sup>+</sup> T cells was determined by carboxyfluorescein succinimidyl ester (CFSE) staining. Clinically, 75% of aGVHD and 78% of cGVHD patients responded to ECP therapy. Moreover, our data show that aGVHD, cGVHD patients and healthy donors (HDs) present distinct NK patterns: aGVHD patients have a higher frequency of CD56<sup>bri</sup> NK subsets with stronger NKG2D and CD62L expression, while CD56<sup>−</sup>CD16<sup>+</sup> NK cells with higher expression of CD57 and CD11b stand out as a signature population for cGVHD. ECP therapy could significantly decrease CD56<sup>bri</sup>CD16<sup>−</sup> NK cells with shifting the quality from a cytotoxic to a regulatory pattern and additionally mature CD56<sup>dim</sup> NK cells via upregulation of CD57 in complete responding aGVHD patients. Moreover, ECP could keep the anti-viral and anti-leukemic effects intact via maintaining specialized anti-viral/leukemic CD57<sup>+</sup>NKG2C<sup>+</sup>CD56<sup>dim</sup> NK cells as well as remaining the quality and quantity of cytokine release by NK cells. The proliferative capacity of effector cells remained constant over ECP therapy. In conclusion, ECP represents an attractive option to treat GVHD without compromising anti-viral/leukemic effects. Shaping of CD56<sup>bri</sup> NK cell compartment by downregulating the cytotoxic subset while upregulating the regulatory subset contributes to the mechanisms of ECP therapy in aGVHD.</p>