Peripheral CD4 T-cell depletion is not sufficient to prevent ischemic acute renal failure

Transplantation. 2005 Sep 15;80(5):643-9. doi: 10.1097/01.tp.0000173396.07368.55.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / immunology
  • Acute Kidney Injury / prevention & control*
  • Acute Kidney Injury / therapy
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Caspase 1 / metabolism
  • Delayed Graft Function / immunology
  • Delayed Graft Function / prevention & control*
  • Delayed Graft Function / therapy
  • Genes, T-Cell Receptor alpha / immunology
  • Interleukin-18 / metabolism
  • Ischemia / immunology
  • Ischemia / prevention & control
  • Kidney Transplantation*
  • Lymphocyte Depletion*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains

Substances

  • Antibodies, Monoclonal
  • Interleukin-18
  • monoclonal antibody GK1.5
  • Caspase 1