Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 203, Issue 2, Pages 329-339Publisher
OXFORD UNIV PRESS
DOI: 10.1111/cei.13539
Keywords
dendritic cells; extracorporeal photopheresis; rodent; tolerance
Categories
Funding
- Von Behring-Rontgen-Stiftung [64-0019]
- German Jose Carreras leukemia foundation [AH06-01]
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Extracorporeal photopheresis (ECP) acts through antigen-presenting dendritic cells (DC) and is influenced by CD11c(+) DC, demonstrating antigen specificity and showing the critical importance of CD11c(+) DC for ECP activity.
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.
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