Role of / and / T cells in renal ischemia-reperfusion injury

Hochegger K, Schätz T, Eller P, Tagwerker A, Heininger D, Mayer G, Rosenkranz AR. Role of / and / T cells in renal ischemia reperfusion injury. Am J Physiol Renal Physiol 293: F741–F747, 2007. First published June 13, 2007; doi:10.1152/ajprenal.00486.2006.—T cells have been implicated in the pathogenesis of renal ischemia-reperfusion injury (IRI). To date existing data about the role of the T cell receptor (Tcr) are contradictory. We hypothesize that the Tcr plays a prominent role in the late phase of renal IRI. Therefore, renal IRI was induced in / , / T cell-deficient and wild-type mice by clamping renal pedicles for 30 min and reperfusing for 24, 48, 72, and 120 h. Serum creatinine increased equally in all three groups 24 h after ischemia but significantly improved in Tcr-deficient animals compared with wildtype controls after 72 h. A significant reduction in renal tubular injury and infiltration of CD4 T-cells in both Tcr-deficient mice compared with wild-type controls was detected. Infiltration of / T cells into the kidney was reduced in / T cell-deficient mice until 72 h after ischemia. In contrast, / T cell infiltration was equal in wild-type and / T cell-deficient mice, suggesting an interaction between / and / T cells. Data from / T cell-deficient mice were confirmed by in vivo depletion of / T cells in C57BL/6 mice. Whereas / T cell-deficient mice were still protected after 120 h, / T cell-deficient mice showed a “delayed wild-type phenotype” with a dramatic increase in kidney-infiltrating / , Tcr-expressing CD4 T-cells. This report provides further evidence that / T cells are major effector cells in renal IRI, whereas / T cells play a role as mediator cells in the first 72 h of renal IRI.