Protective effect of T cell depletion in murine renal ischemia-reperfusion injury.

Abstract

Ischemia-reperfusion injury (IRI) is the main cause of acute renal failure in both allograft and native kidney. Studies using T cell knockout mice have established an important role for T cells in renal IRI. T cell depletion strategies are effective in human allograft rejection. However, it is not known whether those are effective in renal IRI. Therefore, the effect of T cell depletion in a murine model of renal IRI using well-characterized antibodies (Abs) that have been effective in preventing experimental allograft rejection was studied. T cell depleting Abs to CD4 (GK1.5), CD8 (2.43) or pan-T cells (30.H12) were purified from hybridoma culture supernatant. Thymectomized C57BL/6 mice, treated with different combinations of T cell depleting Abs, underwent 30 min of bilateral renal IRI, followed by assessment of renal function, structure, and degree of T cell depletion in spleen, lymph nodes, and peripheral blood by flow cytometry. Mice given both GK1.5 and 2.43 had considerable CD4 and CD8 cell depletion but no protection of renal function after ischemia-reperfusion (I/R) as measured by the rise in serum creatinine. However, when GK1.5 and 2.43 was administered combined with 30.H12, which more effectively depleted CD4 T cell numbers, a significant protection of renal function and structure was observed after I/R. Antibody combinations did not significantly alter other leukocyte populations. These data demonstrate that T cell depletion can improve the course of experimental renal IRI. However, more aggressive T cell depletion strategies were required compared with that needed to prevent experimental allograft rejection.