Peripheral CD4 T-cell depletion is not sufficient to prevent ischemic acute renal failure
S Faubel, D Ljubanovic, B Poole, B Dursun, Z He… - …, 2005 - journals.lww.com
Transplantation, 2005•journals.lww.com
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 …
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 …
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 α-chain deficient (TCRα−/−) mice. TCRα−/− mice lack the α 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, TCRα−/− 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 (eg, macrophages or NK cells) as a source of IL-18 and mediator of ischemic ARF warrants further investigation.
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