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Department of Pediatrics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
High frequencies of EBV-specific CD8+ T cells have been
detected during acute EBV infection, yet persistent infection
inevitably results. To address this issue, we characterized the
phenotype and function of epitope-specific CD8+ T cell
populations from presentation with acute through latent infection.
Considerable phenotypic and functional heterogeneity within, as well as
between, two different epitope-specific populations was observed over
time following acute infection. B7 EBV-encoded nuclear Ag
(EBNA)-3A-specific CD8+ T cells expressed only CD45RO from
acute through latent EBV infection. A2 BMLF-1-specific
CD8+ T cells expressed CD45RO during acute infection and
either CD45RA or CD45RO during latent EBV infection. This difference in
CD45 isoform expression between the two epitope-specific populations
did not translate into differences in perforin content, the ability to
produce IFN-
, or the ability to proliferate in response to Ag in
vitro. In individuals with latent EBV infection, the frequencies of A2
BMLF-1- or B7 EBNA-3A-specific CD8+ T cells that expressed
CD45RA, CD45RO, CD62 ligand, CCR7, and perforin were stable over
time. However, the expression of CD62 ligand and CCR7 was significantly
higher among EBNA-3A-specific CD8+ T cells than among
BMLF-1-specific CD8+ T cells. Further work is necessary to
understand how phenotypic and functional differences between EBV
epitope-specific CD8+ T cells are related to the biology of
the virus and to the equilibrium between the virus and the host during
persistent infection.
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