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Am J Transplant. 2015 Sep;15(9):2431-42. doi: 10.1111/ajt.13288. Epub 2015 May 5.

CMV Primary Infection Is Associated With Donor-Specific T Cell Hyporesponsiveness and Fewer Late Acute Rejections After Liver Transplantation.

Author information

1
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
2
Department of Liver Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
3
Department of Internal Medicine, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
4
Department of Virology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
5
Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Abstract

Viral infections, including cytomegalovirus (CMV), abrogate transplantation tolerance in animal models. Whether this also occurs in humans remains elusive. We investigated how CMV affects T cells and rejection episodes after liver transplantation (LT). Phenotype and alloreactivity of peripheral and allograft-infiltrating T cells from LT patients with different CMV status were analyzed by flow cytometry. The association of CMV status with early and late acute rejection was retrospectively analyzed in a cohort of 639 LT patients. CMV-positivity was associated with expansion of peripheral effector memory T cell subsets after LT. Patients with CMV primary infection showed donor-specific CD8(+) T cell hyporesponsiveness. While terminally differentiated effector memory cells comprised the majority of peripheral donor-specific CD8(+) T cells in CMV primary infection patients, they were rarely present in liver allografts. Retrospective analysis showed that R(-) D(+) serostatus was an independent protective factor for late acute rejection by multivariate Cox regression analysis (hazard ratio [HR] = 0.18, 95% CI = 0.04-0.86, p = 0.015). Additionally, CMV primary infection patients showed the highest Vδ1/Vδ2 γδ T cell ratio, which has been shown to be associated with operational tolerance after LT. In conclusion, our data suggest that CMV primary infection may promote tolerance to liver allografts, and CMV status should be considered when tapering or withdrawing immunosuppression.

KEYWORDS:

Cytomegalovirus (CMV); T cell biology; donor-specific hyporesponsiveness; hepatology; immunobiology; infection and infectious agents; infectious disease; liver transplantation; rejection; science; tolerance; translational research; viral

PMID:
25943855
DOI:
10.1111/ajt.13288
[Indexed for MEDLINE]
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