title: Effect of T cells on vascular permeability in early ischemic acute kidney injury in mice.
abstract: Although previous studies have demonstrated that microvascular dysfunction and inflammation occur in ischemia-reperfusion injury (IRI), the underlying mechanisms are poorly understood. We hypothesized that T cells could mediate renal vascular permeability (RVP) during IRI. We evaluated renal vascular permeability by extravasation of Evans blue dye from the kidney in CD3, CD4 or CD8 T cell deficient mice as well as in TNF receptor knock out mice in our mouse model of kidney ischemia-reperfusion injury. In wild type mice, RVP was significantly increased at 3 h, peaked at 6 h and declined by 24 h after ischemia. Immunohistochemistry revealed that CD3(+) T cells trafficked into ischemic kidney at 1 h and peaked at 6 h. Gene microarray analysis demonstrated that endothelial-related genes including TNF-alpha were up-regulated in ischemic kidney. The production of TNF-alpha and IFN-gamma protein was increased in CD3 and CD4 T cells from the blood and kidney after ischemia. The rise in RVP after ischemia in wild type mice was attenuated in CD3, CD4 or CD8 T cell deficient mice as well as in TNF receptor knock out mice. The attenuation of RVP in CD3 T-cell deficient mice after ischemia was restored by adoptive transfer of T cells from WT mice. Our data demonstrate that T cells directly contribute to the increased RVP after kidney ischemia-reperfusion, potentially through T cell cytokine production.
authors.affiliation: Division of Nephrology, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205, USA. manchang@jhmi.edu
authors.forename: Manchang
authors.initials: M
authors.lastname: Liu
authors.forename: Chu-Chun
authors.initials: CC
authors.lastname: Chien
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Grigoryev
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Gandolfo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Colvin
authors.forename: Hamid
authors.initials: H
authors.lastname: Rabb