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Retrovirology. 2014 Dec 14;11:116. doi: 10.1186/s12977-014-0116-6.

Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression.

Author information

1
Section of Virology, Department of Medicine, Imperial College London, London, W2 1PG, UK. a.rowan@imperial.ac.uk.
2
Department of Bioregulatory Medicine, Graduate School of Medicine, Ehime University, and Ehime University Proteomedicine Research Center, Toh-on city, Ehime, Japan. suemori@m.ehime-u.ac.jp.
3
Department of Bioregulatory Medicine, Graduate School of Medicine, Ehime University, and Ehime University Proteomedicine Research Center, Toh-on city, Ehime, Japan. yunarief@m.ehime-u.ac.jp.
4
Department of Bioregulatory Medicine, Graduate School of Medicine, Ehime University, and Ehime University Proteomedicine Research Center, Toh-on city, Ehime, Japan. yasukawa@m.ehime-u.ac.jp.
5
Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. yuetsu@s4.dion.ne.jp.
6
Section of Virology, Department of Medicine, Imperial College London, London, W2 1PG, UK. g.p.taylor@imperial.ac.uk.
7
Section of Virology, Department of Medicine, Imperial College London, London, W2 1PG, UK. c.bangham@ipmerial.ac.uk.

Abstract

BACKGROUND:

Immunogenetic evidence indicates that cytotoxic T lymphocytes (CTLs) specific for the weak CTL antigen HBZ limit HTLV-1 proviral load in vivo, whereas there is no clear relationship between the proviral load and the frequency of CTLs specific for the immunodominant antigen Tax. In vivo, circulating HTLV-1-infected cells express HBZ mRNA in contrast, Tax expression is typically low or undetectable. To elucidate the virus-suppressing potential of CTLs targeting HBZ, we compared the ability of HBZ- and Tax-specific CTLs to lyse naturally-infected cells, by co-incubating HBZ- and Tax-specific CTL clones with primary CD4(+) T cells from HLA-matched HTLV-1-infected donors. We quantified lysis of infected cells, and tested whether specific virus-induced host cell surface molecules determine the susceptibility of infected cells to CTL-mediated lysis.

RESULTS:

Primary infected cells upregulated HLA-A*02, ICAM-1, Fas and TRAIL-R1/2 in concert with Tax expression, forming efficient targets for both HTLV-1-specific CTLs and CTLs specific for an unrelated virus. We detected expression of HBZ mRNA (spliced isoform) in both Tax-expressing and non-expressing infected cells, and the HBZ26-34 epitope was processed and presented by cells transfected with an HBZ expression plasmid. However, when coincubated with primary cells, a high-avidity HBZ-specific CTL clone killed significantly fewer infected cells than were killed by a Tax-specific CTL clone. Finally, incubation with Tax- or HBZ-specific CTLs resulted in a significant decrease in the frequency of cells expressing high levels of HLA-A*02.

CONCLUSIONS:

HTLV-1 gene expression in primary CD4(+) T cells non-specifically increases susceptibility to CTL lysis. Despite the presence of HBZ spliced-isoform mRNA, HBZ epitope presentation by primary cells is significantly less efficient than that of Tax.

PMID:
25499803
PMCID:
PMC4282740
DOI:
10.1186/s12977-014-0116-6
[Indexed for MEDLINE]
Free PMC Article

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