Publication Date:
2011-11-18
Description:
Abstract 2176 Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory therapy by exposing isolated white blood cells to photoactive 8-MOP (psoralen) and UVA radiation (PUVA) for refractory acute and chronic graft-versus-host disease (GVHD). Although the effects of PUVA treatment on immune system remain poorly characterized, we have reported that bone marrow-derived dendritic cells (BM-DCs), which are generated from bone marrow cells plus GM-CSF, acquired tolerogenicity by PUVA-treatment in mice. In mixed lymphocyte reaction (MLR) assays, strong tolerogenicity was observed when adding PUVA-DCs generated from the same strain of stimulator cells, or responder cells, or even from third-party (Figure 1) strain into MLR mixture. That is, the PUVA-treated DCs have tolerogenic function in a MHC-independent manner (52nd ASH), in part, due to the reduced expression levels of CD80 and CD86, both of which are costimulatory molecules for T cell activation. To clarify the mechanisms of how PUVA-treated DCs induce tolerogenicity in further detail, we performed MLR with the addition of neutralizing antibodies against IL-10 or TGF-β1 or both, which have immunosuppressive effects. Neutralization of immunosuppressive cytokines had no effects on MLR. We then hypothesized that cell-to-cell contact between PUVA-DCs and alloreactive T-cells was needed to mediate the regulatory effect. To this end, we performed MLR using transwell to prevent cell-to cell contact. MLR was not suppressed when transwell was used, suggesting that PUVA-DCs dominantly regulates the alloreaction in a cell contact-dependent manner. Next we compared the expression of the indoleamine 2,3-dioxygenase (IDO), which induces T-cell anergy by tryptophan depletion and by the production of metabolic byproducts collectively known as kynurenines, by real-time PCR between PUVA-DCs and BM-DCs. An increased IDO gene transcription level was observed in PUVA-DCs about 5 times more than in BM-DCs (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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