title: Peripheral CD4 T-cell depletion is not sufficient to prevent ischemic acute renal failure.
abstract: BACKGROUND
  Ischemia reperfusion injury leading to acute renal failure (ARF) and delayed graft function is an important problem in organ transplantation. CD4+ T cells, essential for transplant rejection, may mediate ischemic ARF. We have demonstrated that the caspase-1 mediated production of IL-18 is pathogenic in ischemic ARF in mice. A potential source of IL-18 in ischemic ARF is the CD4+ T cell. We therefore examined the effect CD4+ T cell depletion on the development of ischemic ARF and the activation of IL-18.
  
  
  METHODS
  Functional and histological correlates were examined in two groups of mice with ischemic ARF: 1) CD4 T-cell depleted with the antibody GK1.5, and 2) T-cell receptor alpha-chain deficient (TCRalpha -/-) mice. TCRalpha -/- mice lack the alpha chain of the T-cell receptor and therefore lack functional CD4+ and CD8+ T cells.
  
  
  RESULTS
  Flow cytometry of lymph nodes and immunohistochemistry of kidneys demonstrated complete depletion of CD4+ T cells in mice with ischemic ARF treated with GK 1.5. CD4+ T-cell depletion did not confer functional (serum creatinine, BUN and FITC-labeled inulin clearance) or histological protection against ischemic ARF. Likewise, TCRalpha -/- mice were not protected against ischemic ARF. Renal caspase-1 activity and IL-18 protein were similar in CD4+ T-cell depleted and wild-type postischemic reperfusion.
  
  
  CONCLUSIONS
  Ischemic ARF can occur in the absence of classical T-cell function. The evaluation of other inflammatory mediators (e.g., macrophages or NK cells) as a source of IL-18 and mediator of ischemic ARF warrants further investigation.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, 80262, USA. Sarah.Faubel@uchsc.edu
authors.forename: Sarah
authors.initials: S
authors.lastname: Faubel
authors.forename: Danica
authors.initials: D
authors.lastname: Ljubanovic
authors.forename: Brian
authors.initials: B
authors.lastname: Poole
authors.forename: Belda
authors.initials: B
authors.lastname: Dursun
authors.forename: Zhibin
authors.initials: Z
authors.lastname: He
authors.forename: Susan
authors.initials: S
authors.lastname: Cushing
authors.forename: Hilary
authors.initials: H
authors.lastname: Somerset
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Gill
authors.forename: Charles L
authors.initials: CL
authors.lastname: Edelstein
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D051799:Delayed Graft Function / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D019673:Genes, T-Cell Receptor alpha / Q000276:immunology; D020382:Interleukin-18 / Q000378:metabolism; D007511:Ischemia / Q000276:immunology / Q000517:prevention & control; D016030:Kidney Transplantation; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
chemical_list: D000911:Antibodies, Monoclonal; D020382:Interleukin-18; C106577:monoclonal antibody GK1.5; D020170:Caspase 1