Donor Macrophage Depletion from CMV-Latently Infected Hearts Abrogates CMV-Accelerated Chronic Rejection.
1Department of Surgery, OHSU, Portland, OR
2VGTI, OHSU, Hillsboro, OR
Meeting: 2017 American Transplant Congress
Abstract number: B27
Keywords: Cytomeglovirus, Heart, Rejection
Session Information
Session Name: Poster Session B: Acute and Chronic Rejection
Session Type: Poster Session
Date: Sunday, April 30, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Purpose: Latent donor CMV infection has been shown to accelerate chronic rejection (CR) in a heterotopic rat heart transplant model. CMV latency is associated with an influx of macrophages (macs) and T cells into cardiac tissue. We sought to determine whether the depletion of macs from CMV+ donor allografts using clodronate-laden liposomes would reduce CR.
Methods: Male F344 rats were infected with Rat CMV (RCMV) 9 months prior to organ procurement to establish latent RCMV infection. Three days prior to organ procurement donor rats were treated with PBS, liposomes or clodronate (n=10 rats/group). Mac depletion was confirmed by flow cytometry and immunohistochemistry. Donor hearts from the treated rats were heterotopically transplanted into CMV-naïve Lewis recipients. Post-op treatment with Cyclosporine prevented acute rejection. The time to rejection and extent of graft vasculopathy was monitored. CMV reactivation was assessed by antibody seroconversion and viral load at the time of rejection.
Results:
Clodronate treatment resulted in the depletion of tissue resident macs but not T or B cells from latently infected hearts. Treatment significantly delayed the mean time to graft rejection from 61 days to 84 days post transplant (p=0.002; Figure 1), and reduced the severity of graft vessel disease. Macrophage depletion did not affect recipient seroconversion as all recipients seroconverted to CMV after transplant.
Conclusions: Our study represents a novel approach to the pre-transplant treatment of donors. Donor macrophage depletion with clodronate liposomes resulted in delayed CMV-mediated accelerated CR and reduced graft vascular disease. Clodronate treatment did not prevent recipient CMV infection suggesting mechanisms independent of direct viral pathogenesis.
CITATION INFORMATION: Burg J, Andoh T, Haese N, Jones I, Orloff S, Streblow D. Donor Macrophage Depletion from CMV-Latently Infected Hearts Abrogates CMV-Accelerated Chronic Rejection. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Burg J, Andoh T, Haese N, Jones I, Orloff S, Streblow D. Donor Macrophage Depletion from CMV-Latently Infected Hearts Abrogates CMV-Accelerated Chronic Rejection. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-macrophage-depletion-from-cmv-latently-infected-hearts-abrogates-cmv-accelerated-chronic-rejection/. Accessed May 9, 2025.« Back to 2017 American Transplant Congress