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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1340-1352
Number of pages13
JournalJournal of Clinical Immunology
Volume32
Issue number6
DOIs
Publication statusPublished - 2012 Dec 1
Externally publishedYes

Fingerprint

Stem Cell Transplantation
Lymphoma
Leukemia
Clone Cells
T-Lymphocytes
Adult T Cell Leukemia Lymphoma
Human T-lymphotropic virus 1
Bone Marrow
T-Cell Antigen Receptor
Tissue Donors
Transplants
Graft vs Host Disease
Virus Replication
Immunotherapy

Keywords

  • Adult T cell leukemia/lymphoma
  • cytotoxic T cell
  • human T cell lymphotropic virus type 1
  • T cell receptor repertoire
  • tax

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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

In: Journal of Clinical Immunology, Vol. 32, No. 6, 01.12.2012, p. 1340-1352.

Research output: Contribution to journalArticle

Tanaka, Y, Nakasone, H, Yamazaki, R, Wada, H, Ishihara, Y, Kawamura, K, Sakamoto, K, Ashizawa, M, Machishima, T, Sato, M, Terasako, K, Kimura, SI, Kikuchi, M, Okuda, S, Kako, S, Kanda, J, Tanihara, A, Nishida, J & Kanda, Y 2012, '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', Journal of Clinical Immunology, vol. 32, no. 6, pp. 1340-1352. https://doi.org/10.1007/s10875-012-9729-5
Tanaka, Yukie ; Nakasone, Hideki ; Yamazaki, Rie ; Wada, Hidenori ; Ishihara, Yuko ; Kawamura, Koji ; Sakamoto, Kana ; Ashizawa, Masahiro ; Machishima, Tomohito ; Sato, Miki ; Terasako, Kiriko ; Kimura, Shun Ichi ; Kikuchi, Misato ; Okuda, Shinya ; Kako, Shinichi ; Kanda, Junya ; Tanihara, Aki ; Nishida, Junji ; Kanda, Yoshinobu. / 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. In: Journal of Clinical Immunology. 2012 ; Vol. 32, No. 6. pp. 1340-1352.
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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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T1 - 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

AU - Tanaka, Yukie

AU - Nakasone, Hideki

AU - Yamazaki, Rie

AU - Wada, Hidenori

AU - Ishihara, Yuko

AU - Kawamura, Koji

AU - Sakamoto, Kana

AU - Ashizawa, Masahiro

AU - Machishima, Tomohito

AU - Sato, Miki

AU - Terasako, Kiriko

AU - Kimura, Shun Ichi

AU - Kikuchi, Misato

AU - Okuda, Shinya

AU - Kako, Shinichi

AU - Kanda, Junya

AU - Tanihara, Aki

AU - Nishida, Junji

AU - Kanda, Yoshinobu

PY - 2012/12/1

Y1 - 2012/12/1

N2 - 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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KW - human T cell lymphotropic virus type 1

KW - T cell receptor repertoire

KW - tax

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