CD11c+ dendritic cells mediate antigen-specific suppression in extracorporeal photopheresis.
H HacksteinA KalinaB DornI S KeilN BaalG MichelC BrendelA NeubauerT JakobGregor BeinPublished in: Clinical and experimental immunology (2020)
Extracorporeal photopheresis (ECP) represents one of the most widespread and effective cell therapies for graft-versus-host disease and other T cell-mediated disorders. However, the key factors affecting the therapeutic efficacy of ECP remain unclear. We hypothesized that therapeutic effects are mediated by ECP-treated antigen-presenting dendritic cells (DC). To test this hypothesis, we used the experimental model of contact hypersensitivity (CHS). The ECP's therapeutic activity improved when the total cell dose of the ECP-treated cells was increased. We used different haptens during sensitization to demonstrate that the anti-inflammatory activity of ECP is antigen-specific. This confirmed the hypothesis that professional antigen-presenting cells are involved in the mode of action. Also, the ECP's therapeutic activity was abrogated by the depletion of CD11c+ DC, which represents fewer than 1% of all the ECP-exposed cells. Finally, we confirm the critical importance of CD11c+ DC for ECP activity by showing that only a few purified CD11c+ DC are sufficient to mediate its therapeutic effect. The finding that ECP-treated, physiological antigen-presenting DC alone mediate antigen-specific modulation of a pathological immune response may result in better-targeted interventions when treating patients.
Keyphrases
- dendritic cells
- immune response
- induced apoptosis
- cell cycle arrest
- regulatory t cells
- newly diagnosed
- endoplasmic reticulum stress
- single cell
- nk cells
- ejection fraction
- cell death
- case report
- cell therapy
- mesenchymal stem cells
- inflammatory response
- prognostic factors
- pi k akt
- patient reported outcomes
- patient reported