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Critical Role of Lymphocytes in Hepatic Ischemia/Reperfusion Injury


, : Critical Role of Lymphocytes in Hepatic Ischemia/Reperfusion Injury. FASEB Journal 18(4-5): Abst 441 6

Hepatic ischemia/reperfusion (I/R) injury is thought to result from oxidant stress and neutrophil-dependent mechanisms. Previous reports have suggested that CD4+ lymphocytes may contribute to this response by regulating the liver accumulation of neutrophils. We examined whether lymphocyte populations were recruited into the liver and whether nude or CD4-/- mice had an altered I/R injury response. Male wild-type mice underwent 90 minutes of partial hepatic ischemia and up to 8 hours of reperfusion. Within 1 hour of reperfusion there were increases in the numbers of CD4+ T cells, extrathymic T cells and NK cells. In nude mice, which lack thymically-derived T cells, we observed significant reductions in neutrophil accumulation and liver injury after 8 hours of reperfusion. In CD4-/- mice, which lack CD4+ T cells, there was a significant reduction in neutrophil accumulation, but significant increase in liver injury. These alterations were independent of any changes in production of TNF. The data suggest that various lymphocyte subsets are rapidly recruited to the liver after reperfusion and that these cells directly modulate neutrophil accumulation and the injury response. In addition, CD4+ T cells appear to function in a protective, regulatory fashion to limit hepatocellular injury.This work was supported by NIH grants DK56029 and HL72552.

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