Dendritic cell deficiency in the blood of kidney transplant patients on long-term immunosuppression: results of a prospective matched-cohort study.
Evidence from in vitro studies suggests that immunosuppressive drugs interfere with key functions of dendritic cells (DCs), but the in vivo relevance of these findings is elusive. We prospectively analyzed the major DC precursor subsets in the blood of kidney transplant recipients on long-term immunosuppression (> or =1 year). A total of 87 patients were compared to 87 age- and sex-matched controls. Total DC numbers and the precursor subsets, myeloid type 1 DCs, myeloid type 2 DCs (mDC1, mDC2) and plasmacytoid DCs (pDCs) were identified by four color flow cytometry. Long-term immunosuppression was associated with significant reduction of all major DC subsets in comparison to healthy controls (mDC1 p < 0.001; mDC2 p < 0.0001; two-tailed Mann-Whitney U-test) with the strongest negative impact on pDCs (p < 0.00001). In contrast, total leukocyte numbers were not significantly affected. Analysis of the relative impact of different agents revealed a significant impact of prednisolone on pDCs (p = 0.009) and mDCs2 (p = 0.006). The functional relevance of pDC deficiency was confirmed independently by Interferon-alpha analysis after Toll-like receptor 7 (p < or = 0.001) and 9 (p < 0.05) stimulation. These results indicate for the first time a profound negative impact of long-term immunosuppression on major DC subsets in kidney transplant recipients. DC deficiency may have important implications with respect to viral infections and tumor development.
Hackstein
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H
Department for Internal Medicine, Justus-Liebig University, Giessen, Germany. Holger.Hackstein@immunologie.med.uni-giessen.de
Renner
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FC
Bohnert
A
A
Nockher
A
A
Frommer
T
T
Bein
G
G
Weimer
R
R
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000328:Adult; D017951:Antigen Presentation / Q000187:drug effects; D002478:Cells, Cultured; D015331:Cohort Studies; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects*; D011446:Prospective Studies; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D011239:Prednisolone