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Long-Term Persistence of Limited HTLV-I Tax-specific Cytotoxic T Cell Clones in a Patient with Adult T Cell Leukemia/Lymphoma after Allogeneic Stem Cell Transplantation

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Abstract

Purpose

Adult T cell leukemia/lymphoma (ATL) is a highly aggressive malignancy of T cells caused by human T cell lymphotropic virus type 1 (HTLV-1). Recent clinical studies have suggested that allogeneic stem cell transplantation (HSCT) improves the clinical course of ATL by harnessing a graft-versus-ATL effect, and that donor-derived HTLV-1 Tax-specific CD8+ cytotoxic T cells (CTLs) contribute to the graft-versus-ATL effect after HSCT. However, little is known about the immunological characteristics of Tax-specific CTLs in ATL patients who underwent HSCT.

Methods

We serially analyzed frequencies, differentiation, functions and clonal dynamics of Tax-specific CTLs in paired samples of peripheral blood (PB) and bone marrow (BM) from an ATL patient after HSCT at the single-cell level. We used flowcytometric and single-cell T cell receptor (TCR) repertoire analysis methods without culture steps.

Results

Donor-derived Tax-specific CTLs effectively suppressed HTLV-1 replication in both PB and BM at least during chronic graft-versus-host disease after HSCT. Furthermore, Tax-specific CTLs had comparable properties between BM and PB, except for preferential accumulation in BM rather than PB. Tax-specific CTLs persistently existed as less-differentiated CD45RA-CCR7- effector memory CTLs based on predominant phenotypes of CD27+, CD28+/− and CD57+/−. Our approach using single-cell TCR repertoire analysis method showed highly restricted oligoclonal responses of Tax-specific CTLs, and TCR BV7- or BV30- expressing two predominant CTL clones persistently existed and maintained strong cytotoxic activities against HTLV-1 in both PB and BM over three years after HSCT.

Conclusions

These findings about Tax-specific CTLs provide insights into future directions for studies on immunotherapy against ATL.

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Acknowledgments

This research was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor and Welfare of Japan. This study was subsidized by JKA through its promotion funds from KEIRIN RACE.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya-ku, Saitama, Saitama, 330-8503, Japan

    Yukie Tanaka, Hideki Nakasone, Rie Yamazaki, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Masahiro Ashizawa, Tomohito Machishima, Miki Sato, Kiriko Terasako, Shun-ichi Kimura, Misato Kikuchi, Shinya Okuda, Shinichi Kako, Junya Kanda, Aki Tanihara, Junji Nishida & Yoshinobu Kanda

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Correspondence to Yoshinobu Kanda.

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Tanaka, Y., Nakasone, H., Yamazaki, R. et al. Long-Term Persistence of Limited HTLV-I Tax-specific Cytotoxic T Cell Clones in a Patient with Adult T Cell Leukemia/Lymphoma after Allogeneic Stem Cell Transplantation. J Clin Immunol 32, 1340–1352 (2012). https://doi.org/10.1007/s10875-012-9729-5

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