MethodsMice. nu/nu mice (B6.Cg-Foxn1 nu )and C57BL/6 wild-type littermates were purchased from The Jackson Laboratory (Bar Harbor, Maine, USA). The two main defects of 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.
More than one-third of the patients with steroid-insensitive AR had evidence of AHR, often resistant to antilymphocyte therapy. Most cases (95%) with DSA at the time of rejection had widespread C4d deposits in peritubular capillaries, suggesting a pathogenic role of the circulating alloantibody. Combined DSA testing and C4d staining provides a useful approach for the early diagnosis of AHR, a condition that often necessitates a more intensive therapeutic rescue regimen.
By pathologic analysis, renal tumors are more common in the pre-transplant ESRD population than previously reported (using radiologic methods). Our study also identifies risk factors for their occurrence. This may prove useful in designing screening studies for renal tumors in this patient population.
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