NK cells do not mediate renal injury in murine adriamycin nephropathy

Abstract

In adriamycin nephropathy (AN), a model of chronic proteinuric renal injury, the absence of functional B and T cells with residual natural killer (NK) cells, and macrophages in severe combined immunodeficient (SCID) mice results in more severe disease than in immunocompetent mice. We have recently shown expression of the stimulatory NK cell molecule NKG2D and its ligand RAE-1 in the adriamycin (ADR) kidney. Therefore, we sought to determine the role of NK cells in AN. We used anti-asialo GM1 NK cell depletion in immunocompetent BALB/c mice with AN, and also compared AN in immunodeficient SCID mice and immunodeficient nonobese diabetic (NOD)-SCID mice (that have impaired NK cell function). The number of NK cells was increased in AN in BALB/c mice compared with normal controls. NK cell depletion or reduction of NK function in NOD-SCID mice did not affect the severity of disease. In both wild type and immunodeficient models, ADR upregulated RAE-1 in the kidney. High levels of Class I major histocompatibility complex molecules were found in both models of AN. In conclusion, NK cells do not play a significant role in AN.

CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease

“…Others have shown a direct effect of Treg on antigen-presenting cells (24,25). Recently, an effect of Treg on NK cells was demonstrated (26); however, we showed recently that NK cells are not important in the murine AN (27), so it is unlikely that such an interaction explains the protective effect of CD4 ϩ CD25 ϩ Treg in our study.…”

Depletion of γδ T Cells Exacerbates Murine Adriamycin Nephropathy

“…However, we have demonstrated an absence of NK cell recruitment and function in AN (39). AN can be induced in SCID mice, yet in this mouse, there are NK cells but no ␣␤ or ␥␦ T cells.…”

Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression

“…13 In this lupus nephritis model, Spada et al 13 reported an accumulation of NK cells (NKp46 þ cells) with activated phenotype and increased functional capacity (elevated IFN-g production) in diseased kidneys compared with kidneys from prediseased mice, concluding that they play a pathogenic role in the disease process. In contrast, a study by Zheng et al 14 has suggested that NK cells do not play a role in Adriamycin-induced nephropathy in mice. These conflicting findings may result from the differing mouse models analyzed and highlight potential problems with extrapolating murine findings to human native kidney disease.…”