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

DʼOrsogna, L.J.A., van Besouw, N.M., van der Meer-Prins, E.M.W., van der Pol, P., Franke-van Dijk, M., Zoet, Y.M., van der Slik, A., Weimar, W., van Kooten, C., Mulder, A., Roelen, D.L., Doxiadis, I.I.N. and Claas, F.H.J. (2011) Vaccine-Induced Allo-HLA–Reactive Memory T Cells in a Kidney Transplantation Candidate. Transplantation, 91 (6). pp. 645-651.

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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.

Publication Type: Journal Article
Publisher: Wolters Kluwer Health
Copyright: © 2017 Wolters Kluwer Health, Inc.
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