Virus-Specific CD8+ T Cells Cross-Reactive to Donor-Alloantigen Are Transiently Present in the Circulation of Kidney Transplant Recipients Infected with CMV and/or EBV

K. M. Heutinck*, S. L. Yong, L. Tonneijck, H. Van Den Heuvel, N. C. Van Der Weerd, K. A.M.I. Van Der Pant, F. J. Bemelman, F. H.J. Claas, I. J.M. Ten Berge

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

T cells play a dual role in transplantation: They mediate transplant rejection and are crucial for virus control. Memory T cells generated in response to pathogens can cross-react to alloantigen, a phenomenon called heterologous immunity. Virus-specific CD8+ T cells cross-reacting to donor-alloantigen might affect alloimmune responses and hamper tolerance induction following transplantation. Here, we longitudinally studied these cross-reactive cells in peripheral blood of 25 kidney transplant recipients with a cytomegalovirus and/or Epstein-Barr virus infection. Cross-reactive T cells were identified by flow cytometry as virus-specific T cells that proliferate in response to donor cells in a mixed-lymphocyte reaction. In 13 of 25 patients, we found cross-reactivity to donor cells for at least 1 viral epitope before (n = 7) and/or after transplantation (n = 8). Cross-reactive T cells were transiently present in the circulation, and their precursor frequency did not increase following transplantation or viral infection. Cross-reactive T cells expressed interferon-γ and CD107a in response to both alloantigen and viral peptide and resembled virus-specific T cells in phenotype and function. Their presence was not associated with impaired renal function, proteinuria, or rejection. In conclusion, virus-specific T cells that cross-react to donor-alloantigen are transiently detectable in the circulation of kidney transplant recipients.

Original languageEnglish
Pages (from-to)1480-1491
Number of pages12
JournalAmerican Journal of Transplantation
Volume16
Issue number5
DOIs
Publication statusPublished - 1 May 2016

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