Dendritic cells activated by lipopolysaccharide after dexamethasone treatment induce donor-specific allograft hyporesponsiveness.

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Publication year
2006Source
Transplantation, 81, 10, (2006), pp. 1451-1459ISSN
Publication type
Article / Letter to editor

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Organization
Nephrology
Tumorimmunology
Journal title
Transplantation
Volume
vol. 81
Issue
iss. 10
Page start
p. 1451
Page end
p. 1459
Subject
N4i 1: Pathogenesis and modulation of inflammation; N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 1: Immunity, infection and tissue repair; NCMLS 2: Immune Regulation; NCMLS 3: Tissue engineering and pathology; ONCOL 3: Translational research; UMCN 1.4: Immunotherapy, gene therapy and transplantation; UMCN 5.4: Renal disordersAbstract
BACKGROUND: Immature dendritic cells (imDC) can prolong allograft survival in murine transplantation models. Recent data indicate that semi-mature or alternatively activated DC (aaDC) may be even more tolerogenic. METHODS: We compared the phenotype and regulatory capacity of: a) imDC, cultured in the presence of dexamethasone (DEX), b) mature DC (matDC), activated with LPS, and c) aaDC, activated with LPS after pretreatment with DEX. RESULTS: As compared to imDC, aaDCs displayed a slight upregulation of CD40 while expression levels of MHC-II and CD86 remained low. The production of proinflammatory cytokines, in particular IL-12, by aaDC was much lower than by matDC while both produced similar amounts of the regulatory cytokine IL-10 leading to an increased IL-10/IL-12 ratio for aaDC. After infusion of donor type aaDCs, responder cells isolated from the recipient mice showed donor-specific hyporesponsiveness to restimulation by matDC. Infusion of matDC was immunogenic, while imDC induced partial hyporesponsiveness. Importantly, pretreatment with donor type aaDC (but not imDC) resulted in prolonged survival of a completely MHC-mismatched heart allograft. CONCLUSIONS: Alternatively activated DC are more efficacious than the classical imDC in the regulation of the alloimmune response, which may be related to a distinct cytokine profile characterized by an increased IL-10/IL12 ratio.
This item appears in the following Collection(s)
- Academic publications [202563]
- Electronic publications [100704]
- Faculty of Medical Sciences [79925]
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