Nkt Cell Activation Mediates Neutrophil Ifn- Production and Renal Ischemia-Reperfusion Injury

Li, L.; Huang, L.; Sung, S..J.; Lobo, P.I.; Brown, M.G.; Gregg, R.K.; Engelhard, V.H.; Okusa, M.D.

The Journal of Immunology 178(9): 5899-5911


DOI: 10.4049/jimmunol.178.9.5899
Accession: 068490630

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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 flow 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-gamma-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 (Jalpha18(-/-)), 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-gamma-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-gamma.