title: NKT cell activation mediates neutrophil IFN-gamma production and renal ischemia-reperfusion injury.
abstract: 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.
authors: Department of Medicine, Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
authors: Li
authors: L
authors: Li
authors: Liping
authors: L
authors: Huang
authors: Sun-sang J
authors: SS
authors: Sung
authors: Peter I
authors: PI
authors: Lobo
authors: Michael G
authors: MG
authors: Brown
authors: Randal K
authors: RK
authors: Gregg
authors: Victor H
authors: VH
authors: Engelhard
authors: Mark D
authors: MD
authors: Okusa
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D039481:CD11b Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology*; D019707:Receptors, Chemokine / Q000032:analysis; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039481:CD11b Antigen; D007371:Interferon-gamma; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D019707:Receptors, Chemokine; D000099192:CD69 Antigens; C503133:Gr-1 protein, mouse