Recipient Immunity to Murine Cytomegalovirus Influences Natural Killer Cell Responses in Infected Renal Allografts

M. Shimamura,¹ M. Li,¹ B. Chen,² J. George.²

¹Pediatric Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL
²Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham.

Meeting: 2015 American Transplant Congress

Abstract number: A7

Keywords: Cytomeglovirus, Kidney transplantation, Natural killer cells

Session Information

Session Name: Poster Session A: Acute Allograft Rejection

Session Type: Poster Session

Date: Saturday, May 2, 2015

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Exhibit Hall E

BACKGROUND: Human cytomegalovirus (CMV) is associated epidemiologically with renal allograft loss, but the impact of recipient CMV immunity upon graft survival is unclear. Natural killer (NK) cells control acute CMV infection whereas CD8 cells control viral reactivation, but their impact in the CMV infected allograft is unknown.

PURPOSE: To define NK and CD8 CTL activation in recipient positive murine CMV infected renal allografts.

METHODS: Kidneys from BALB/c donor mice were transplanted into C57BL/6 recipients with cyclosporine immunosuppression. Donors (D+) and recipients (R+) were infected with murine CMV (MCMV) prior to transplant. Recipients received either low dose MCMV (R+, 1×10² plaque-forming units [pfu]) or high dose (R++, 1×10⁴ pfu) with serologic confirmation of infection. Uninfected recipients (D+/R-) served as controls for experimental D+/R+ and D+/R++ groups (n=6-8/group). At 14 days post-transplant, organs were analyzed by cytokine flow cytometry for interferon-γ (IFNγ)+ and granzyme B (GrB)+ NK cells (CD3-/NKp46+) and for cytotoxic T cells (CD8+/CD62lo/IFNγhi). Groups were compared using the one-way analysis of variance (ANOVA) and the Student's t-test.

RESULTS: D+/R+ grafts contained greater quantities of both IFNγ+ (2174+/-609 cells/g) and GrB+ (9427+/-3296 cells/g) NK cells compared to D+/R- grafts (955+/-372 cells/g and 2533+/-781 cells/g [p=0.04]). Compared to D+/R+ grafts, D+/R++ grafts had fewer IFNγ+ (484+/-132 cells/g)(p=0.03) and GrB+ (1061+/-424 cells/g)(p=0.04) NK cells. D+/R+ grafts also had more abundant CD8+CTLs (20240+/-4699 cells/g) than D+/R++ grafts (5666+/-1849 cells/g)(p=0.02). Systemically, liver NK cell quantities were similar among groups, but liver CTLs were greater in both D+/R+ (477+/-128 cells/g) and D+/R++ (775+/-137 cells/g) compared to D+/R- animals (319+/-80 cells/g)(p=0.04), consistent with memory CD8 responses.

CONCLUSIONS: NK and CTL responses against the infected allograft varied depending on the recipient MCMV infecting dose. Low-dose recipients had higher intragraft NK and CTL responses, whereas high-dose infected recipients had attenuated responses. The graft-specific differences were not observed systemically. These results suggest that in the CMV immune recipient, variable host responses to the infected allograft could contribute to clinically observed differences in graft outcome.

To cite this abstract in AMA style:

Shimamura M, Li M, Chen B, George J. Recipient Immunity to Murine Cytomegalovirus Influences Natural Killer Cell Responses in Infected Renal Allografts [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/recipient-immunity-to-murine-cytomegalovirus-influences-natural-killer-cell-responses-in-infected-renal-allografts/. Accessed November 21, 2024.

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