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

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.

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.

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.

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.