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Longitudinal analysis of frequency and reactivity of epstein–barr virus‐specific T lymphocytes and their association with intermittent viral reactivation
Author(s) -
Vogl Bastian A.,
Fagin Ursula,
Nerbas Linda,
Schlenke Peter,
Lamprecht Peter,
Jabs Wolfram J.
Publication year - 2012
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.22258
Subject(s) - elispot , virology , immunology , virus , viral load , epstein–barr virus , viremia , cd8 , biology , epitope , t cell , immune system , antigen
Persistent Epstein–Barr virus (EBV) infection is controlled tightly by virus‐specific T cells. EBV infection is reactivated intermittently over time, even in apparently healthy carriers. Changes in frequency and reactivity of memory T cells, particularly of CD8 + origin, have not been assessed in this context. It is hypothesized that viral reactivation is facilitated by diminished EBV‐specific T‐cell immunity. To this end, blood samples from 14 healthy donors were collected at irregular time intervals for a period of about 1 year. Samples were screened for both EBV plasma viremia and increases in viral load in PBMCs as parameters of EBV reactivation. PBMCs were subject to IFN‐γ ELISPOT analysis using the autologous EBV‐transformed lymphoblastoid cell line (EBV‐LCL) or appropriate HLA class I‐restricted EBV peptides as stimulators. Frequencies of epitope‐specific CD8 + T cells were monitored further using HLA tetramers and flow cytometry. Twelve of 14 donors exhibited signs of asymptomatic EBV reactivation. Viral reactivation was accompanied by either substantially decreased IFN‐γ responses against autologous EBV‐LCL (eight of 12 study participants) and/or increased responses against particular EBV peptides (six of 12 donors). In seven persons with HLA‐A2 and/or ‐B8 alleles numbers of HLA tetramer‐positive CD8 + T cells also varied over time, but showed no correlation to episodes of detectable viral activity. In summary, IFN‐γ reactivity of EBV‐specific T cells is not constant. Viral reactivation is detected preferably at times of diminished EBV‐LCL‐specific cellular immunity. However, increased reactivity of single immunodominant CD8 + EBV‐specific T‐cell clones may occur in response to virus replication. J. Med. Virol. 84:119–131, 2011. © 2011 Wiley Periodicals, Inc.