Vaccine-Induced Allo-HLA-Reactive Memory T Cells in a Kidney Transplantation Candidate

Loyd J.A. D'Orsogna*, Nicole M. van Besouw, Ellen M.W. van der Meer-Prins, P (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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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-gamma 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.
Original languageEnglish
Pages (from-to)645-651
Number of pages7
JournalTransplantation
Volume91
Issue number6
DOIs
Publication statusPublished - 27 Mar 2011

Research programs

  • EMC MM-04-39-05

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