NKT cell activation mediates neutrophil IFN-γ production and renal eschemia-reperfusion injury

Previous work has shown that ischemia-reperfusion (IR) injury (IRI) is dependent on CD4⁺ T cells from naive mice acting within 24 h. We hypothesize that NKT cells are key participants in the early innate response in IRI. Kidneys from C57BL/6 mice were subjected to IRI (0.5, 1, 3, and 24 h of reperfusion). After 30 min of reperfusion, we observed a significant increase in CD4⁺ cells (145% of control) from single-cell kidney suspensions as measured by low cytometry. A significant fraction of CD4⁺ T cells expressed the activation marker, CD69⁺, and adhesion molecule, LFA-1^high. Three hours after reperfusion, kidney IFN-γ- producing cells were comprised largely of GR-1⁺CD11b⁺ neutrophils, but also contained CD1d-restricted NKT cells. Kidney IRI in mice administered Abs to block CD1d, or deplete NKT cells or in mice deficient of NKT cells (Jα18^-/-), was markedly attenuated. These effects were associated with a significant decrease in renal infiltration and, in activation of NKT cells, and a decrease in IFN-γ-producing neutrophils. The results support the essential role of NKT cells and neutrophils in the innate immune response of renal IRI by mediating neutrophil infiltration and production of IFN-γ.