Longitudinal analysis of frequency and reactivity of Epstein-Barr virus-specific T lymphocytes and their association with intermittent viral reactivation
– Source: Journal of Medical Virology, Jan 2012
By BA Vogl, et al.
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-? 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-? responses against autologous EBV-LCL (8 of 12 study participants) and/or increased responses against particular EBV peptides (6 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-? 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.
Source: Journal of Medical Virology, Jan 2012;84(1):119-31. PMID: 22095540, by Vogl BA, Fagin U, Nerbas L, Schlenke P, Lamprecht P, Jabs WJ. Department of Medicine I, University of Luebeck School of Medicine, Luebeck, Germany.