title: 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.
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.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.|Renal Transplant Unit, Department of Nephrology, Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: K M
authors.initials: KM
authors.lastname: Heutinck
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.|Renal Transplant Unit, Department of Nephrology, Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: S L
authors.initials: SL
authors.lastname: Yong
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Tonneijck
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van den Heuvel
authors.affiliation: Renal Transplant Unit, Department of Nephrology, Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: N C
authors.initials: NC
authors.lastname: van der Weerd
authors.affiliation: Renal Transplant Unit, Department of Nephrology, Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: K A M I
authors.initials: KA
authors.lastname: van der Pant
authors.affiliation: Renal Transplant Unit, Department of Nephrology, Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: Bemelman
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: F H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Renal Transplant Unit, Department of Nephrology, Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: I J M
authors.initials: IJ
authors.lastname: Ten Berge
mesh_terms: D000956:Antigens, Viral; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D005919:Glomerular Filtration Rate; D006085:Graft Survival; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma; D007519:Isoantigens / Q000097:blood / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology* / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D011379:Prognosis; D012307:Risk Factors; D014019:Tissue Donors; D066027:Transplant Recipients; D014184:Transplantation, Homologous
chemical_list: D000956:Antigens, Viral; D007519:Isoantigens; D007371:Interferon-gamma