• DOI:10.1111/ajt.13288
• Corpus ID: 5348557

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

@article{Shi2015CMVPI,
  title={CMV Primary Infection Is Associated With Donor‐Specific T Cell Hyporesponsiveness and Fewer Late Acute Rejections After Liver Transplantation},
  author={X.L. Shi and E L D de Mare-Bredemeijer and {\"O}zlem Tapirdamaz and Bettina E Hansen and Rogier van Gent and Margo J H van Campenhout and Shanta Mancham and Nicolle H. R. Litjens and Michiel G H Betjes and Annemiek A. van der Eijk and Q. Xia and Luc J.W. van der Laan and Jeroen de Jonge and Herold Johnny Metselaar and Jaap Kwekkeboom},
  journal={American Journal of Transplantation},
  year={2015},
  volume={15}
}

• X.L. Shi, E. D. de Mare-Bredemeijer, +12 authors J. Kwekkeboom
• Published 1 September 2015
• Medicine, Biology
• American Journal of Transplantation

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.