Monocytes show immunoregulatory capacity on CD4+ T cells in a humanin-vitromodel of extracorporeal photopheresis

Abstract

Summary Extracorporeal photopheresis (ECP) is a widely used immunomodulatory therapy for the treatment of various T cell‐mediated disorders such as cutaneous T cell lymphoma (CTCL), graft‐versus‐host disease (GvHD) or systemic sclerosis. Although clinical benefits of ECP are already well described, the underlying mechanism of action of ECP is not yet fully understood. Knowledge on the fate of CD14+ monocytes in the context of ECP is particularly limited and controversial. Here, we investigated the immunoregulatory function of ECP treated monocytes on T cells in an in‐vitro ECP model. We show that ECP‐treated monocytes significantly induce proinflammatory T cell types in co‐cultured T cells, while anti‐inflammatory T cells remain unaffected. Furthermore, we found significantly reduced proliferation rates of T cells after co‐culture with ECP‐treated monocytes. Both changes in interleukin secretion and proliferation were dependent on cell‐contact between monocytes and T cells. Interestingly, blocking interactions of programmed death ligand 1 (PD‐L1) to programmed death 1 (PD‐1) in the in‐vitro model led to a significant recovery of T cell proliferation. These results set the base for further studies on the mechanism of ECP, especially the regulatory role of ECP‐treated monocytes.

European dermatology forum – updated guidelines on the use of extracorporeal photopheresis 2020 – part 1

“…Reduced proliferation rates of T cells after co-culture with ECP-treated monocytes was dependent on cell-contact between monocytes and T cells. 28 Also, there is evidence that infusion of lymphocytes treated with 8-MOP and UVA light induces CD19+ IL-10+ regulatory B cells and thereby promotes skin allograft survival. 29 The manifestation of acute GvHD (aGvHD) in patients with allogeneic grafts was associated with a low number of T-reg cells.…”

“…In addition, monocytes showed immunoregulatory capacity on CD4+ T cells in a human in vitro model of ECP. Reduced proliferation rates of T cells after co‐culture with ECP‐treated monocytes was dependent on cell‐contact between monocytes and T cells 28 . Also, there is evidence that infusion of lymphocytes treated with 8‐MOP and UVA light induces CD19+ IL‐10+ regulatory B cells and thereby promotes skin allograft survival 29 …”

Extracorporeal Photopheresis: A Case of Immunotherapy Ahead of Its Time

“…The internalization of apoptotic cells may decrease the inflammatory reaction of phagocytes, inhibit the transcription of IL-12 in nonirradiated cells, and induce antigen-specific immunotolerance [77-79]. In vitro priming of T cells with ECP-exposed monocytes increases IFN-γ and IL-17 production but reduces the proliferation capacity of T cells in response to TCR stimulation in a cell contact mechanism regulated by transient PD-1 interactions [80]. Expression of the glucocorticoid-induced leucine zipper (GILZ) (an inhibitor of multiple pathways including NF-κB) is a distinctive characteristic of tolerogenic DC and it is increased by 8-MOP/UVA exposure [81, 82].…”

Extracorporeal Photopheresis (ECP) and the Potential of Novel Biomarkers in Optimizing Management of Acute and Chronic Graft vs. Host Disease (GvHD)

“…The data for the effects of ECP on monocyte cell death are conflicting. While some groups report that monocytes are as susceptible to ECP-induced apoptosis as other PBMC (92)(93)(94), others show marked survival (95)(96)(97) or showed no greater levels of cell death than untreated controls (98,99). The reported preferential survival of monocytes may be facilitated by integrin-mediated survival signals generated through interaction of monocytes with plasma proteins bound to plastic surfaces in the ECP instrument, which subsequently directed differentiation into monocyte-derived dendritic cells (100).…”