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Cellular infiltrates and NF[kappa]B subunit c-Rel signaling in kidney allografts of patients with clinical operational tolerance

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Background: Nuclear factor kappa B (NFκB) plays a potential role in tolerance by orchestrating onset and resolution of inflammation and regulatory T cell differentiation through subunit c-Rel. We characterized cellular infiltrates and expression of NFκB1, c-Rel and its upstream regulators phosphatid...

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Hauptverfasser: Becker, Luis Eduardo (VerfasserIn) , Biazotto, Fúvia de Oliveira (VerfasserIn) , Conrad, Heike (VerfasserIn) , Schaier, Matthias (VerfasserIn) , Kihm, Lars Philipp (VerfasserIn) , Groß-Weissmann, Marie-Luise (VerfasserIn) , Waldherr, Rüdiger (VerfasserIn) , Bierhaus, Angelika (VerfasserIn) , Nawroth, Peter Paul (VerfasserIn) , Zeier, Martin (VerfasserIn) , Morath, Christian (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: October 15, 2012
In: Transplantation
Year: 2012, Jahrgang: 94, Heft: 7, Pages: 729-737
ISSN:1534-6080
DOI:10.1097/TP.0b013e31826032be
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1097/TP.0b013e31826032be
Verlag, Volltext: https://insights.ovid.com/crossref?an=00007890-201210150-00010
Volltext
Verfasserangaben:Luis E. Becker, Fúvia de Oliveira Biazotto, Heike Conrad, Matthias Schaier, Lars P. Kihm, Marie-luise Gross-weissmann, Rüdiger Waldherr, Angelika Bierhaus, Peter P. Nawroth, Martin Zeier, and Christian Morath
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Zusammenfassung:Background: Nuclear factor kappa B (NFκB) plays a potential role in tolerance by orchestrating onset and resolution of inflammation and regulatory T cell differentiation through subunit c-Rel. We characterized cellular infiltrates and expression of NFκB1, c-Rel and its upstream regulators phosphatidylinositol 3-kinase/RAC-alpha serine/threonine kinase, in allograft biopsies from patients with spontaneous clinical operational tolerance (COT). Methods: Paraffin-fixed kidney allograft biopsies from 40 patients with COT (n=4), interstitial rejection (IR; n=12), borderline changes (BC; n=12), and long-term allograft function without rejection (NR; n=12) were used in the study. Cellular infiltrates and immunohistochemical expression of key proteins of the NFκB pathway were evaluated in the cortical tubulointerstitium and in cellular infiltrates using digital image analysis software. Results were given as mean±SEM. Results: Biopsies from patients with COT exhibited a comparable amount of cellular infiltrate to IR, BC, and NR (COT, 191±81; IR, 291±62; BC, 178±45; and NR, 210±42 cells/mm2) but a significantly higher proportion of forkhead box P3-positive cells (COT, 11%±1.7%; IR, 3.5%±0.70%; BC, 3.4%±0.57%; and NR, 3.7%±0.78% of infiltrating cells; P=0.02). c-Rel expression in cellular infiltrates was significantly elevated in IR, BC, and NR when analyzing the number of positive cells per mm2 (P=0.02) and positive cells per infiltrating cells (P=0.04). In contrast, tubular PI3K and c-Rel expression were significantly higher in IR and BC but not in NR compared with COT (P=0.03 and P=0.006, respectively). With RAC-alpha serine-threonine kinase, similar tendencies were observed (P=0.2). Conclusions: Allografts from COT patients show significant cellular infiltrates but a distinct expression of proteins involved in the NFκB pathway and a higher proportion of forkhead box P3-positive cells.
Beschreibung:Publication date: 2012/10/15
Gesehen am 06.11.2018
Beschreibung:Online Resource
ISSN:1534-6080
DOI:10.1097/TP.0b013e31826032be

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