BACKGROUND AND OBJECTIVES: Forkhead box P3 regulatory T cells control inflammatory responses, but it remains unclear whether they inhibit brain death-initiated inflammation and tissue injury in deceased kidney donors. DESIGN, SETTING, PARTICIPANTS, MEASUREMENT: To study the actions of regulatory T cells at various stages of the donation and transplantation procedure, forkhead box P3, regulatory and inflammatory cytokine expression, and tissue injury markers were determined in time 0 kidney biopsies from deceased and living donors. Additionally, the interaction between forkhead box P3+ T cells and kidney injury molecule-1 by activated primary tubular epithelial cells was studied. RESULTS: After cold storage, the deceased donor kidneys expressed the higher mRNA levels of kidney injury molecule-1 and CD3ε. In these samples, the inflammatory cytokines IL-8 and IFN-γ and markers associated with regulation (forkhead box P3, TGF-β, and IL-10) were highly expressed compared with living donor kidneys. Correlations were found between mRNA expression levels of forkhead box P3 and kidney injury molecule-1 and forkhead box P3 and IFN-γ. Immunohistochemical analysis confirmed the presence of forkhead box P3+ T cells in donor kidneys. Renal function (analyzed by serum creatinine levels) at the first week posttransplantation correlated with kidney injury molecule-1 and forkhead box P3 mRNA levels. In vitro studies showed that kidney injury molecule-1 expression by primary tubular epithelial cells was 63% (mean) lower when cocultured with regulatory T cells compared with control T cells. CONCLUSIONS: These results show that donor forkhead box P3+ T cells infiltrate the deceased donor kidney, where they may control inflammatory and injury responses.
BACKGROUND AND OBJECTIVES:Forkhead box P3 regulatory T cells control inflammatory responses, but it remains unclear whether they inhibit brain death-initiated inflammation and tissue injury in deceased kidney donors. DESIGN, SETTING, PARTICIPANTS, MEASUREMENT: To study the actions of regulatory T cells at various stages of the donation and transplantation procedure, forkhead box P3, regulatory and inflammatory cytokine expression, and tissue injury markers were determined in time 0 kidney biopsies from deceased and living donors. Additionally, the interaction between forkhead box P3+ T cells and kidney injury molecule-1 by activated primary tubular epithelial cells was studied. RESULTS: After cold storage, the deceased donor kidneys expressed the higher mRNA levels of kidney injury molecule-1 and CD3ε. In these samples, the inflammatory cytokines IL-8 and IFN-γ and markers associated with regulation (forkhead box P3, TGF-β, and IL-10) were highly expressed compared with living donor kidneys. Correlations were found between mRNA expression levels of forkhead box P3 and kidney injury molecule-1 and forkhead box P3 and IFN-γ. Immunohistochemical analysis confirmed the presence of forkhead box P3+ T cells in donor kidneys. Renal function (analyzed by serum creatinine levels) at the first week posttransplantation correlated with kidney injury molecule-1 and forkhead box P3 mRNA levels. In vitro studies showed that kidney injury molecule-1 expression by primary tubular epithelial cells was 63% (mean) lower when cocultured with regulatory T cells compared with control T cells. CONCLUSIONS: These results show that donorforkhead box P3+ T cells infiltrate the deceased donor kidney, where they may control inflammatory and injury responses.
Authors: Estelle Bettelli; Yijun Carrier; Wenda Gao; Thomas Korn; Terry B Strom; Mohamed Oukka; Howard L Weiner; Vijay K Kuchroo Journal: Nature Date: 2006-04-30 Impact factor: 49.962
Authors: S Yoshida; A Haque; T Mizobuchi; T Iwata; M Chiyo; T J Webb; L A Baldridge; K M Heidler; O W Cummings; T Fujisawa; J S Blum; D D Brand; D S Wilkes Journal: Am J Transplant Date: 2006-04 Impact factor: 8.086
Authors: Niamh Ni Choileain; Malcolm MacConmara; Yan Zang; Thomas J Murphy; John A Mannick; James A Lederer Journal: J Immunol Date: 2006-01-01 Impact factor: 5.422
Authors: Laurie E Harrington; Robin D Hatton; Paul R Mangan; Henrietta Turner; Theresa L Murphy; Kenneth M Murphy; Casey T Weaver Journal: Nat Immunol Date: 2005-10-02 Impact factor: 25.606
Authors: Halina Offner; Sandhya Subramanian; Susan M Parker; Chunhe Wang; Michael E Afentoulis; Anne Lewis; Arthur A Vandenbark; Patricia D Hurn Journal: J Immunol Date: 2006-06-01 Impact factor: 5.422
Authors: Francine B C Lemos; Jan N M Ijzermans; Pieter E Zondervan; Annemiek M A Peeters; Sandra van den Engel; Wendy M Mol; Willem Weimar; Carla C Baan Journal: J Am Soc Nephrol Date: 2003-12 Impact factor: 10.121
Authors: C Van Kooten; J G Boonstra; M E Paape; F Fossiez; J Banchereau; S Lebecque; J A Bruijn; J W De Fijter; L A Van Es; M R Daha Journal: J Am Soc Nephrol Date: 1998-08 Impact factor: 10.121
Authors: Camila M Mazeti-Felicio; Heloisa C Caldas; Ida M M Fernandes-Charpiot; Camila Z Dezotti; Maria A S F Baptista; Mario Abbud-Filho Journal: Transplant Direct Date: 2017-06-23