BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: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. CONCLUSIONS: 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.
Authors: Amandeep Bajwa; Sang-Kyung Jo; Hong Ye; Liping Huang; Krishna R Dondeti; Diane L Rosin; Volker H Haase; Timothy L Macdonald; Kevin R Lynch; Mark D Okusa Journal: J Am Soc Nephrol Date: 2010-03-25 Impact factor: 10.121
Authors: T K Mehta; M O Hoque; R Ugarte; M H Rahman; E Kraus; R Montgomery; K Melancon; D Sidransky; H Rabb Journal: Transplant Proc Date: 2006-12 Impact factor: 1.066
Authors: Yang Ju-Rong; Chen Ke-Hong; Huang Kun; Fu Bi-Qiong; Lin Li-Rong; Zhang Jian-Guo; Li Kai-Long; He Ya-Ni Journal: J Am Soc Nephrol Date: 2016-07-27 Impact factor: 10.121