Th17 and NK Responses Are Differentially Induced in Renal Allografts According to Recipient Murine Cytomegalovirus Dose and Strain
1Center for Vaccines and Immunity and Dept. of Pediatric Infectious Diseases, The Research Institute at Nationwide Children's Hospital and The Ohio State University, Columbus, OH
2Depts. of Pediatric Infectious Diseases, Pathology, and Genetics, University of Alabama at Birmingham, Birmingham, AL.
Meeting: 2018 American Transplant Congress
Abstract number: 97
Keywords: Cytomeglovirus, Kidney transplantation, Mice, Natural killer cells
Session Information
Session Name: Concurrent Session: Acute Rejection
Session Type: Concurrent Session
Date: Sunday, June 3, 2018
Session Time: 4:30pm-6:00pm
Presentation Time: 4:42pm-4:54pm
Location: Room 6A
Purpose: To study the impact of cytomegalovirus (CMV) recipient positive (R+) serostatus upon renal allograft injury, murine CMV (MCMV) D+/R+ kidney transplants using recipients infected with varying MCMV doses and strains were assessed for immune mechanisms of graft injury.
Methods: BALB/c to C57BL/6 renal transplants were performed with cyclosporine immunosuppression. 12 weeks pre-transplant, donors were infected with MCMV [Delta]m157 at 104 plaque-forming units [pfu]; recipients with MCMV[Delta]m157 at low dose [102 pfu] or high dose [104 pfu], or with MCMV wild-type (MCMVwt) at 104 pfu. Allografts were analyzed by cytokine flow cytometry (CFC), cytokine array (Legendplex), and histopathology (24-point scale). Allograft-derived T cells were stimulated with peptides for either inflationary (M38) or noninflationary (M45) epitopes for CFC. Groups were compared using the Student's t-test and ANOVA, accepting significance at p<0.05.
Results: Low-dose recipients had greater interferon-gamma+ (IFN-γ+) NK cells compared to high-dose recipients (2174±609 cells/g vs. 484±132 cells/g, p=0.03), greater intragraft CD4+ Th17 cells (18569±2263 cells/g vs. 6569±2555 cells/g, p<0.01), and higher Th17-associated cytokines including IL-1β, IL-6, IL-23, IL-17A, and GM-CSF. High dose recipient allografts had greater TNF-α+ NK cells than low-dose recipients (37656±10501 vs. 15647±2529, p<0.05). Different-strain D+/R+ allografts had greater histopathologic injury than same-strain transplants (damage scores 14.3±1.8 vs. 11.9±1.4, p=0.0318), and more granzyme B+ (GzB+) NK cells (8086±2453 cells/g vs. 1063±442 cells/g, p=0.02). All D+/R+ groups had similar numbers of intragraft virus-specific CD8+ CTLs, and no differences in responses to inflationary and noninflationary epitopes.
Conclusions: In this model, recipient virus dose and strain influenced characteristics of immune-mediated renal allograft injury, with significant differences in Th17 and NK cells, but no differences in antiviral CD8+ CTL responses. These results suggest that mechanisms of R+ CMV-induced allograft injury may differ according to conditions of the recipient's primary infection.
CITATION INFORMATION: Shimamura M., Li M., Boddeda S., Chen B., Zeng Q., Schoeb T., Velazquez V. Th17 and NK Responses Are Differentially Induced in Renal Allografts According to Recipient Murine Cytomegalovirus Dose and Strain Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Shimamura M, Li M, Boddeda S, Chen B, Zeng Q, Schoeb T, Velazquez V. Th17 and NK Responses Are Differentially Induced in Renal Allografts According to Recipient Murine Cytomegalovirus Dose and Strain [abstract]. https://atcmeetingabstracts.com/abstract/th17-and-nk-responses-are-differentially-induced-in-renal-allografts-according-to-recipient-murine-cytomegalovirus-dose-and-strain/. Accessed May 16, 2025.« Back to 2018 American Transplant Congress