NK-Activating MCMV Strain Is Associated with Increased Murine Renal Transplant Injury.
1Vaccines and Immunity, Pediatric Infectious Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, OH
2Pediatric Infectious Diseases, Cardiothoracic Surgery, Nephrology, University of Alabama at Birmingham, Birmingham, AL
3Pathology and Genetics, University of Alabama at Birmingham, Birmingham, AL.
Meeting: 2016 American Transplant Congress
Abstract number: 349
Keywords: Cytomeglovirus, Kidney transplantation, Natural killer cells
Session Information
Session Name: Concurrent Session: Pathways of Allograft Rejection: Animal Models
Session Type: Concurrent Session
Date: Monday, June 13, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 5:06pm-5:18pm
Location: Room 310
Background: CMV contributes to inferior longterm kidney transplant survival. In a murine model, NK cells infiltrate MCMV infected renal allografts in greater numbers than in uninfected grafts, and NK depletion reduces histologic injury. NK transcripts are enriched in early biopsies of grafts with late failure, suggesting that early NK activation contributes to late graft failure.
Purpose: To define the impact of NK activating and evading MCMV strains upon virus-induced allograft injury.
Methods: MCMV infected BALB/c to C57BL/6 kidney transplants were performed with cyclosporine immunosuppression. Recipients were infected pre-transplant with either the NK-activating wild-type MCMV Smith strain (MCMVwt), or the NK-evading MCMV Smith[Delta]m157 (MCMV[Delta]157). Donors were infected with MCMV[Delta]157. At 14 days post-transplant, organs were analyzed by cytokine flow cytometry (cells/g) for interferon-γ (IFNγ)+ and granzyme B (GrB)+ NK cells (CD3-/NKp46+) and for cytotoxic T cells (CD8+/CD62lo/IFNγhi). Histologic graft injury was graded blindly on a 27 point scale by a veterinary pathologist. Statistical analysis was performed using one-way analysis of variance (ANOVA) and the Student's t-test.
Results: MCMVwt recipients had greater GrB+ NK cell infiltrates compared to MCMV[Delta]157 recipients (8086±2453 vs. 1061±424, p=0.02), but similar IFNγ+ NK infiltrates (365±103 vs. 556±101, p>0.05). MCMVwt and MCMV[Delta]157 liver NK infiltrates resembled allografts for GzB (14323±2323 vs. 2495±667, p<0.001) and IFNγ (1229±376 vs. 1352±451, p>0.05). The CD8+CTL responses of MCMVwt recipients were increased compared to MCMV[Delta]157 recipients (allograft: 44380±7146 vs. 5666±1849, p<0.001) (liver: 5087±669 vs. 775±137, p<0.001). Histologic injury was more severe in the MCMVwt group (14.29±0.69) compared to the MCMV[Delta]157 group (10.83±1.12)(p=0.02).
Conclusions: Recipient infection with a NK-activating MCMV strain induces host NK and CD8 activation associated with greater allograft injury, compared to infection with a NK evading MCMV strain. We conclude that (1) NK activation by CMV contributes to allograft damage, and (2) allograft injury is more severe in recipients receiving a transplant infected with a different CMV strain.
CITATION INFORMATION: Shimamura M, Li M, Chen B, George J, Schoeb T. NK-Activating MCMV Strain Is Associated with Increased Murine Renal Transplant Injury. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Shimamura M, Li M, Chen B, George J, Schoeb T. NK-Activating MCMV Strain Is Associated with Increased Murine Renal Transplant Injury. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/nk-activating-mcmv-strain-is-associated-with-increased-murine-renal-transplant-injury/. Accessed May 11, 2025.« Back to 2016 American Transplant Congress