title: Vaccine-induced allo-HLA-reactive memory T cells in a kidney transplantation candidate.
abstract: BACKGROUND
  Allo-human leukocyte antigen (HLA) reactivity by naturally acquired viral-specific memory T cells is common. However, the effect of successful vaccination on the alloreactive memory T-cell repertoire is unclear. We hypothesized that vaccination could specifically induce allo-HLA-reactive memory T cells.
  
  
  METHODS
  A varicella-zoster virus (VZV) immediate early 62 (IE62)-specific CD8 memory T-cell clone was single cell sorted from a VZV seronegative renal transplant candidate after response to live attenuated varicella vaccination. To analyze the allo-HLA reactivity, the VZV IE62-specific T-cell clone was tested against HLA-typed target cells and target cells transfected with HLA molecules, in both cytokine production and cytotoxicity assays.
  
  
  RESULTS
  The varicella vaccine-induced VZV IE62-specific T-cell clone specifically produced interferon-γ when stimulated with HLA-B*55:01-expressing Epstein-Barr virus-transformed B cells and HLA-B*55:01-transfected K562 cells (single HLA antigen expressing cell line [SALs]) only. The clone also demonstrated specific cytolytic effector function against HLA-B*55:01 SALs and phytohemagglutinin blasts. Cytotoxicity assays using proximal tubular epithelial cell and human umbilical vein endothelial cell targets confirmed the kidney tissue specificity of the allo-HLA-B*55:01 reactivity, and the relevance of the cross-reactivity to clinical kidney transplantation. The results also suggest that molecular mimicry, and not bystander proliferation, is the mechanism underlying vaccine-induced alloreactivity.
  
  
  CONCLUSIONS
  Varicella vaccination generated a de novo alloreactive kidney cell-specific cytolytic effector memory T cell in a patient awaiting renal transplantation. Vaccination-induced alloreactivity may have important clinical implications, especially for vaccine timing and recipient monitoring.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands. l.j.a.d_orsogna@lumc.nl
authors.forename: Lloyd J A
authors.initials: LJ
authors.lastname: D'Orsogna
authors.forename: Nicole M
authors.initials: NM
authors.lastname: van Besouw
authors.forename: Ellen M W
authors.initials: EM
authors.lastname: van der Meer-Prins
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Pol
authors.forename: Marry
authors.initials: M
authors.lastname: Franke-van Dijk
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Zoet
authors.forename: Arno
authors.initials: A
authors.lastname: van der Slik
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.forename: Arend
authors.initials: A
authors.lastname: Mulder
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D019433:Chickenpox Vaccine / Q000276:immunology*; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007156:Immunologic Memory; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D019433:Chickenpox Vaccine; D006680:HLA Antigens; C074221:IE62 protein, Human herpesvirus 3; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014759:Viral Envelope Proteins