In vitro PUVA treatment triggers calreticulin exposition and HMGB1 release by dying T lymphocytes in GVHD: New insights in extracorporeal photopheresis. Issue 4 (12th March 2019)

• Record Type: Journal Article
• Authors: Coppard, Céline; Hannani, Dalil; Humbert, Marion; Gauthier, Virginie; Plumas, Joel; Merlin, Etienne; Gabert, Françoise; Chaperot, Laurence
• Is Part Of: Journal of clinical apheresis. Volume 34:Issue 4(2019)
• Page Start: 450
• Page End: 460
• Publication Date: 2019-03-12
• Subjects: apoptosis -- damage‐associated molecular patterns -- dendritic cells -- extracorporeal photopheresis -- graft vs host disease; Hemapheresis -- Periodicals; Blood -- Transfusion -- Periodicals; Blood -- Transfusion, Autologous -- Periodicals; Cell separation -- Periodicals; Leukapheresis -- Periodicals; Plasmapheresis -- Periodicals; 615.39
• DOI: 10.1002/jca.21698
• Languages: English
• ISSNs: 0733-2459

Abstract

Abstract: Background: Extracorporeal photopheresis (ECP) is an effective therapy for graft vs host disease (GVHD), based on infusion of UVA‐irradiated and 8 methoxy‐psoralen (PUVA)‐treated leukocytes. Reinfusion of these apoptosing cells affects the functionality of pathogenic T cells through poorly understood immunomodulatory mechanisms. Apoptosis is usually a silent, tolerance‐associated process, but can also be immunogenic, depending on death‐inducers and environmental context. Methods: To understand ECP mechanisms of action, human alloreactive T cells generated in an in vitro model mimicking GVHD were used, as well as primary cells from GVHD patients. Cells were submitted to PUVA treatment and their phenotype and immunogenicity were analyzed, using cell culture and flow cytometry. Results: In vitro PUVA treatment induced the expression of several damage‐associated molecular patterns (DAMPs) by dying T cells (calreticulin, high‐mobility group box‐1, and to a lesser extent heat shock proteins 70 and 90), especially upon T cell activation, leading to their phagocytosis by macrophages and dendritic cells (DCs). Allogeneic DCs preincubated with PUVA treated T cells induced comparable naive T cell proliferation and polarization as control allogeneic DC. Conclusion: Altogether, in our experimental settings, in vitro PUVA‐treatment induces a partially immunogenic phenotype allowing phagocytosis of apoptotic cells by macrophages and DC, however not sufficient to induce dendritic cell maturation and T cell activation. These data refine current models of ECP‐mediated immune modulation and emphasize the need to further analyze PUVA‐treated cell interactions with immune cells.