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

• Verfasst von: Becker, Luis Eduardo [VerfasserIn]
• Verfasst von: Biazotto, Fúvia de Oliveira [VerfasserIn]
• Verfasst von: Conrad, Heike [VerfasserIn]
• Verfasst von: Schaier, Matthias [VerfasserIn]
• Verfasst von: Kihm, Lars Philipp [VerfasserIn]
• Verfasst von: Groß-Weissmann, Marie-Luise [VerfasserIn]
• Verfasst von: Waldherr, Rüdiger [VerfasserIn]
• Verfasst von: Bierhaus, Angelika [VerfasserIn]
• Verfasst von: Nawroth, Peter Paul [VerfasserIn]
• Verfasst von: Zeier, Martin [VerfasserIn]
• Verfasst von: Morath, Christian [VerfasserIn]
• Titel: Cellular infiltrates and NF[kappa]B subunit c-Rel signaling in kidney allografts of patients with clinical operational tolerance
• Verf.angabe: 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
• E-Jahr: 2012
• Jahr: October 15, 2012
• Umfang: 9 S.
• Fussnoten: Publication date: 2012/10/15 ; Gesehen am 06.11.2018
• Titel Quelle: Enthalten in: Transplantation
• Ort Quelle: Hagerstown, Md. : Lippincott Williams & Wilkins, 1963
• Jahr Quelle: 2012
• Band/Heft Quelle: 94(2012), 7, Seite 729-737
• ISSN Quelle: 1534-6080
• DOI: doi:10.1097/TP.0b013e31826032be
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1582627916

Abstract

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.