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

Retrovirology

Charles RM Bangham³  Graham P Taylor³  Yuetsu Tanaka¹  Masaki Yasukawa²  Hiroshi Fujiwara²  Koichiro Suemori²  Aileen G Rowan³ 

[1] Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan;Department of Bioregulatory Medicine, Graduate School of Medicine, Ehime University, and Ehime University Proteomedicine Research Center, Toh-on city, Ehime, Japan;Section of Virology, Department of Medicine, Imperial College London, London W2 1PG, UK

关键词: Fas;    ICAM-1;    HLA;    Tax;    HBZ;    CTL;    Cytotoxic lymphocyte response;    Retrovirus;    HTLV-1;   

Others  :  1151496
DOI  :  10.1186/s12977-014-0116-6

 received in 2014-07-11, accepted in 2014-11-27,  发布年份 2014

【 摘 要 】

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 HBZ_26–34 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.

【 授权许可】

   
2014 Rowan et al.; licensee BioMed Central.

【 图 表 】

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