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.
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Authors | Lloyd 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 |
Journal | Transplantation
(Transplantation)
Vol. 91
Issue 6
Pg. 645-51
(Mar 27 2011)
ISSN: 1534-6080 [Electronic] United States |
PMID | 21283063
(Publication Type: Journal Article)
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Chemical References |
- Chickenpox Vaccine
- HLA Antigens
- IE62 protein, Human herpesvirus 3
- Immediate-Early Proteins
- Trans-Activators
- Viral Envelope Proteins
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Topics |
- 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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