Vaccine-induced allo-HLA-reactive memory T cells in a kidney transplantation candidate.

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.
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.
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.
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.
AuthorsLloyd J A D'Orsogna, Nicole M van Besouw, Ellen M W van der Meer-Prins, Pieter van der Pol, Marry Franke-van Dijk, Yvonne M Zoet, Arno van der Slik, Willem Weimar, Cees van Kooten, Arend Mulder, Dave L Roelen, Ilias I N Doxiadis, Frans H J Claas
JournalTransplantation (Transplantation) Vol. 91 Issue 6 Pg. 645-51 (Mar 27 2011) ISSN: 1534-6080 [Electronic] United States
PMID21283063 (Publication Type: Journal Article)
Chemical References
  • Chickenpox Vaccine
  • HLA Antigens
  • IE62 protein, Human herpesvirus 3
  • Immediate-Early Proteins
  • Trans-Activators
  • Viral Envelope Proteins
  • Chickenpox Vaccine (immunology)
  • Cross Reactions
  • Cytotoxicity, Immunologic
  • HLA Antigens (immunology)
  • Humans
  • Immediate-Early Proteins (immunology)
  • Immunologic Memory
  • Kidney Transplantation (immunology)
  • Male
  • Middle Aged
  • Organ Specificity
  • T-Lymphocytes (immunology)
  • Trans-Activators (immunology)
  • Viral Envelope Proteins (immunology)

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