TY - JOUR
T1 - Identification of the cd4+ T cell as a major pathogenic factor in ischemic acute renal failure
AU - Burne, Melissa J.
AU - Daniels, Frank
AU - El Ghandour, Asmaa
AU - Mauiyyedi, Shamila
AU - Colvin, Robert B.
AU - O'Donnell, Michael P.
AU - Rabb, Hamid
PY - 2001
Y1 - 2001
N2 - 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-γ 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.
AB - 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-γ 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.
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U2 - 10.1172/JCI200112080
DO - 10.1172/JCI200112080
M3 - Article
C2 - 11696572
AN - SCOPUS:0035193573
SN - 0021-9738
VL - 108
SP - 1283
EP - 1290
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 9
ER -