Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure

J Clin Invest. 2001 Nov;108(9):1283-90. doi: 10.1172/JCI12080.


Leukocytes have been implicated in the pathogenesis of ischemic acute renal failure (ARF), but the roles of the individual cell types involved are largely unknown. Recent indirect evidence suggests that T cells may play an important role in a murine model of ARF. In the current study, we found that mice deficient in T cells (nu/nu mice) are both functionally and structurally protected from postischemic renal injury. Reconstitution of nu/nu mice with wild-type T cells restored postischemic injury. We then analyzed the contribution of the individual T cell subsets to postischemic injury and found that mice deficient in CD4(+) T cells, but not mice deficient in CD8(+) T cells, were significantly protected from ARF. Direct evidence for a pathophysiologic role of the CD4(+) T cell was obtained when reconstitution of CD4-deficient mice with wild-type CD4(+) T cells restored postischemic injury. In addition, adoptive transfers of CD4(+) T cells lacking either the costimulatory molecule CD28 or the ability to produce IFN-gamma were inadequate to restore injury phenotype. These results demonstrate that the CD4(+) T cell is an important mediator of ischemic ARF, and targeting this cell may yield novel therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / immunology
  • Acute Kidney Injury / metabolism*
  • Animals
  • CD28 Antigens / biosynthesis
  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Flow Cytometry
  • Immunohistochemistry
  • Interferon-gamma / metabolism
  • Leukocytes / metabolism
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Neutrophils / metabolism
  • Phenotype
  • T-Lymphocytes / immunology
  • Time Factors


  • CD28 Antigens
  • CD4 Antigens
  • CD8 Antigens
  • Interferon-gamma