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Lymphoma

PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients

Leukemia volume 23, pages 375–382 (2009)Cite this article

Abstract

Adult T-cell leukemia/lymphoma (ATLL) develops after infection with human T-cell leukemia virus-1 (HTLV-1) after a long latency period. The negative regulatory programmed death-1/programmed death-1 ligand 1 (PD-1/PD-L1) pathway has been implicated in the induction of cytotoxic T-lymphocyte (CTL) exhaustion during chronic viral infection along with tumor escape from host immunity. To determine whether the PD-1/PD-L1 pathway could be involved in the establishment of persistent HTLV-1 infections and immune evasion of ATLL cells in patients, we examined PD-1/PD-L1 expression on cells from 27 asymptomatic HTLV-1 carriers (ACs) and 27 ATLL patients in comparison with cells from 18 healthy donors. PD-1 expression on HTLV-1-specific CTLs from ACs and ATLL patients was dramatically elevated. In addition, PD-1 expression was significantly higher on CD8+ T cells along with cytomegalovirus (CMV)- and Epstein–Barr virus (EBV)-specific CTLs in ATLL patients compared with ACs and control individuals. Primary ATLL cells in 21.7% of ATLL patients expressed PD-L1, whereas elevated expression was not observed in cells from ACs. Finally, in functional studies, we observed that an anti-PD-L1 antagonistic antibody upregulated HTLV-1-specific CD8+T-cell response. These observations suggest that the PD-1/PD-L1 pathway plays a role in fostering persistent HTLV-1 infections, which may further ATLL development and facilitate immune evasion by ATLL cells.

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Acknowledgements

Research support: This study was supported by a Grant-in-Aid (to NA) from the Japanese Ministry of Health, Labor, and Welfare, and by the Kagoshima University for Frontier Science Research Center Program (to NA). We thank Dr Jeffrey A Medin for a critical reading of the paper, Ms Hokkoku for preparation of clinical samples, and Ms Ariyoshi for HLA typing.

Author information

Author notes

  1. H Fujiwara

    Present address: 5Current address: Ehime University Graduate School of Medicine, Department of Bioregulatory Medicine, Ehime, Japan.,

  2. T Kozako and M Yoshimitsu: These authors contributed equally to this study.

Authors and Affiliations

  1. Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

    T Kozako, I Masamoto, S Horai, Y White, S Suzuki, K Uozumi & N Arima

  2. Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

    T Kozako

  3. Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan

    M Yoshimitsu, H Fujiwara, M Akimoto & K Matsushita

  4. Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Kagoshima, Japan

    C Tei

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  1. T Kozako
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Corresponding author

Correspondence to N Arima.

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This study was carried out at Kagoshima University.

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Kozako, T., Yoshimitsu, M., Fujiwara, H. et al. PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients. Leukemia 23, 375–382 (2009). https://doi.org/10.1038/leu.2008.272

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