Antigen presentation by dendritic cells in renal lymph nodes is linked to systemic and local injury to the kidney

Antigen presentation by dendritic cells in renal lymph nodes is linked to systemic and local injury to the kidney. Dendritic cells (DCs) uniquely serve as conduits between innate and cognate arms of the immune system. The normal kidney contains an extensive population of interstitial DCs but their r...

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Veröffentlicht in:Kidney international 2005-09, Vol.68 (3), p.1096-1108
Hauptverfasser: Dong, Xiangyang, Swaminathan, Sundararaman, Bachman, Lori A., Croatt, Anthony J., Nath, Karl A., Griffin, Matthew D.
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Sprache:eng
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Zusammenfassung:Antigen presentation by dendritic cells in renal lymph nodes is linked to systemic and local injury to the kidney. Dendritic cells (DCs) uniquely serve as conduits between innate and cognate arms of the immune system. The normal kidney contains an extensive population of interstitial DCs but their role in the pathogenesis of acute renal injury is not known. Renal DCs were studied by flow cytometric analysis of collagenase-digested mouse kidneys, by immunohistochemistry, and by immunofluorescence microscopy. In vivo ingestion by DCs of intravenously administered fluorescein isothiocyanate (FITC)-dextran particles was examined. A model antigen system (presentation of ovalbumin-derived peptide to TCR transgenic CD4+ T-cells) was employed to examine the influence of systemic (lipopolysacchride injection) and localized (unilateral renal artery clipping) renal injury on DC-mediated T-cell activation in the renal lymph nodes (RLNs). Renal DCs were shown to constitute the predominant source of T-cell stimulatory capacity within the kidney, and to avidly ingest both filtered and nonfiltered particles. Lipopolysaccharide resulted in disappearance of DCs from the renal interstitium within 48 hours. This was accompanied by increased renal lymph node DCs, some of which contained intracellular Tamm-Horsfall Protein, indicating abnormal trafficking of kidney-specific antigens following renal injury. Lipopolysaccharide enhanced DC-mediated proliferation of ovalbumin-specific CD4+ve T-cells within the draining RLN. Unilateral renal ischemia augmented the capacity for DC-mediated T-cell activation in the lymph nodes draining both the ischemic and nonischemic kidney. Renal DCs respond to systemic or localized acute renal injury by increasing the traffic of protein antigens from kidney to RLN, resulting in a concomitant increased potential for localized activation of antigen-specific CD4+ve T-cells.
ISSN:0085-2538
1523-1755
DOI:10.1111/j.1523-1755.2005.00502.x