PURPOSE: NK cell activation is induced by viral infection and has been associated with renal allograft injury in clinical populations and animal models, so this study was undertaken to determine whether NK depletion ameliorates or exacerbates murine cytomegalovirus-induced allograft injury in a murine transplant model.
Murine CMV (MCMV) infected BALB/c donor kidneys were transplanted orthotopically into uninfected C57BL/6 recipients (D+/R- transplants) with cyclosporine immunosuppression. One cohort was treated with NK-depleting antibodies and compared to a group without NK depletion. At day 14 post-transplant, immune infiltrates were examined by flow cytometry, and viral loads were quantitated by DNA PCR. Histology was scored by a veterinary pathologist blinded to sample identity, using a grading system (0-3, maximum score 27) developed for murine transplants based on the Banff criteria for grading of clinical allograft biopsies.
At day 14 post-transplant, efficacy of NK depletion was confirmed in the transplant kidneys, livers, and spleens by flow cytometric analysis for CD45+/CD3-/NKp46+ cells. Histology showed improved damage scores in NK depleted animals (average score 7.5+/-1.0) compared to NK replete animals (average score 11.83+/-1.4) (p<0.05). However, viral loads were higher in NK depleted animals ((2.8 x 104 copies/g +/-9.6×103) compared to NK replete animals (4.5×102 copies/g +/- 1.2×102) (p<0.01).
NK depletion improves allograft damage despite higher viral loads, suggesting that NK cells may contribute to virus-associated allograft injury. These results are consistent with observations in ganciclovir-treated animals that demonstrate improvement of allograft damage associated with decreased NK cell infiltration; however, ganciclovir treatment decreased the viral loads. The findings in the NK depleted animals suggest a possibility that modulation of antiviral immune responses such as NK activation, even in the presence of virus, may ameliorate viral renal allograft injury.
To cite this abstract in AMA style:Shimamura M, Guo L, George J, Schoeb T, Britt W. NK Depletion Reduces Murine Cytomegalovirus Induced Renal Allograft Injury Despite Increased Viral Loads in a Murine Transplant Model [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/nk-depletion-reduces-murine-cytomegalovirus-induced-renal-allograft-injury-despite-increased-viral-loads-in-a-murine-transplant-model/. Accessed September 27, 2020.
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