BACKGROUND: Extracorporeal photopheresis (ECP) emerged as a promising treatment modality for steroid-refractory graft-versus-host disease (GVHD), which represents a major complication of allogeneic hematopoietic stem-cell transplantation. Dendritic cells (DCs) display an extraordinary capacity to induce T-cell responses and play a crucial role in the initiation and maintainance of GVHD. This study evaluated the direct impact of ECP on the proinflammatory capacity of 6-sulfo LacNAc (slan) DCs, representing a major subpopulation of human blood DCs. METHODS: SlanDCs were isolated from ECP-treated or untreated blood of healthy donors or GVHD patients by immunomagnetic isolation. The maturation of slanDC was determined by flow cytometry. Cytokine production of slanDCs was measured by enzyme-linked immunosorbent assay. SlanDC-mediated T-cell proliferation was evaluated by H-thymidine incorporation. SlanDC-mediated T-cell programming was determined by flow cytometry. RESULTS: ECP efficiently impairs the spontaneous maturation and secretion of proinflammatory tumor necrosis factor-alpha, interleukin-1beta, and interleukin-12 by slanDCs. Furthermore, ECP markedly inhibits slanDC-induced proliferation of CD4 and CD8 T cells and polarization of naïve CD4 T lymphocytes into Th1 cells. CONCLUSIONS: These novel findings indicate that ECP efficiently impairs the proinflammatory capacity of slanDCs, which may represent an important mechanism for the therapeutic efficiency of ECP in GVHD.
BACKGROUND: Extracorporeal photopheresis (ECP) emerged as a promising treatment modality for steroid-refractory graft-versus-host disease (GVHD), which represents a major complication of allogeneic hematopoietic stem-cell transplantation. Dendritic cells (DCs) display an extraordinary capacity to induce T-cell responses and play a crucial role in the initiation and maintainance of GVHD. This study evaluated the direct impact of ECP on the proinflammatory capacity of 6-sulfo LacNAc (slan) DCs, representing a major subpopulation of human blood DCs. METHODS: SlanDCs were isolated from ECP-treated or untreated blood of healthy donors or GVHDpatients by immunomagnetic isolation. The maturation of slanDC was determined by flow cytometry. Cytokine production of slanDCs was measured by enzyme-linked immunosorbent assay. SlanDC-mediated T-cell proliferation was evaluated by H-thymidine incorporation. SlanDC-mediated T-cell programming was determined by flow cytometry. RESULTS: ECP efficiently impairs the spontaneous maturation and secretion of proinflammatory tumor necrosis factor-alpha, interleukin-1beta, and interleukin-12 by slanDCs. Furthermore, ECP markedly inhibits slanDC-induced proliferation of CD4 and CD8 T cells and polarization of naïve CD4 T lymphocytes into Th1 cells. CONCLUSIONS: These novel findings indicate that ECP efficiently impairs the proinflammatory capacity of slanDCs, which may represent an important mechanism for the therapeutic efficiency of ECP in GVHD.
Authors: E Mimiola; O Marini; O Perbellini; A Micheletti; W Vermi; S Lonardi; C Costantini; E Meneghelli; A Andreini; C Bonetto; A Vassanelli; M Cantini; E Zoratti; D Massi; A Zamo'; A Leso; G Quaresmini; F Benedetti; G Pizzolo; M A Cassatella; C Tecchio Journal: Clin Exp Immunol Date: 2014-10 Impact factor: 4.330
Authors: N Rieber; I Wecker; D Neri; K Fuchs; I Schäfer; A Brand; M Pfeiffer; P Lang; W Bethge; O Amon; R Handgretinger; D Hartl Journal: Bone Marrow Transplant Date: 2014-01-27 Impact factor: 5.483
Authors: Francine M Foss; Xin Victoria Wang; Selina M Luger; Opeyemi Jegede; Kenneth B Miller; Edward A Stadtmauer; Theresa L Whiteside; David E Avigan; Randall D Gascoyne; Daniel Arber; Henry Wagner; Roger K Strair; William J Hogan; Kellie A Sprague; Hillard M Lazarus; Mark R Litzow; Martin S Tallman; Sandra J Horning Journal: Transfusion Date: 2020-07-12 Impact factor: 3.157