Single-cell analysis of T-cell receptor repertoire of HTLV-1 tax-specific cytotoxic T cells in allogeneic transplant recipients with adult T-cell leukemia/lymphoma

Yukie Tanaka, Hideki Nakasone, Rie Yamazaki, Ken Sato, Miki Sato, Kiriko Terasako, Shun Ichi Kimura, Shinya Okuda, Shinichi Kako, Kumi Oshima, Aki Tanihara, Junji Nishida, Toshiaki Yoshikawa, Tetsuya Nakatsura, Haruo Sugiyama, Yoshinobu Kanda

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Adult T-cell leukemia (ATL) is a lymphoproliferative malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. Recently, it has been shown that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for ATL, and that HTLV-1 Tax-specific CD8+ cytotoxic T cells (CTL) contribute to the graft-versus-ATL effect. In the present study, we, for the first time, analyzed the T-cell receptor (TCR) repertoire of isolated Tax301-309 (SFHSLHLLF)-specific CTLs in HLA-A*2402+ ATL patients before and after allo-HSCT by single-cell reverse transcription-PCR. The Tax301-309-specific CTLs in bone marrow and peripheral blood showed highly restricted oligoclonal diversity. In addition, a unique conserved amino acid motif of "P-D/P-R" in TCR-β complementarity-determining region 3 in either BV7- or BV18-expressing CTLs was observed not only in all of the samples from ATL patients, but also in samples from the same patient before and after HSCT. Furthermore, the P-D/P-R motif-bearing CTL clones established from peripheral blood samples after HSCT exhibited strong killing activity against the HTLV-1-infected T cells of the patient. CTL clones were not established in vitro from samples prior to allo-HSCT. In addition, CTL clones with a strong killing activity were enriched in vivo after HSCT in the patient. Hence, Tax 301-309-specific CTLs in ATL patients might have a preference for TCR construction and induce strong immune responses against the HTLV-1-infected T cells of patients, which contribute to the graft-versus-ATL effects after allo-HSCT. However, further analyses with a larger number of patients and more frequent sampling after allo-HSCT is required to confirm these findings.

Original languageEnglish
Pages (from-to)6181-6192
Number of pages12
JournalCancer Research
Volume70
Issue number15
DOIs
Publication statusPublished - 2010 Aug 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Single-cell analysis of T-cell receptor repertoire of HTLV-1 tax-specific cytotoxic T cells in allogeneic transplant recipients with adult T-cell leukemia/lymphoma'. Together they form a unique fingerprint.

  • Cite this

    Tanaka, Y., Nakasone, H., Yamazaki, R., Sato, K., Sato, M., Terasako, K., Kimura, S. I., Okuda, S., Kako, S., Oshima, K., Tanihara, A., Nishida, J., Yoshikawa, T., Nakatsura, T., Sugiyama, H., & Kanda, Y. (2010). Single-cell analysis of T-cell receptor repertoire of HTLV-1 tax-specific cytotoxic T cells in allogeneic transplant recipients with adult T-cell leukemia/lymphoma. Cancer Research, 70(15), 6181-6192. https://doi.org/10.1158/0008-5472.CAN-10-0678