TY - JOUR
T1 - 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
AU - Tanaka, Yukie
AU - Nakasone, Hideki
AU - Yamazaki, Rie
AU - Sato, Ken
AU - Sato, Miki
AU - Terasako, Kiriko
AU - Kimura, Shun Ichi
AU - Okuda, Shinya
AU - Kako, Shinichi
AU - Oshima, Kumi
AU - Tanihara, Aki
AU - Nishida, Junji
AU - Yoshikawa, Toshiaki
AU - Nakatsura, Tetsuya
AU - Sugiyama, Haruo
AU - Kanda, Yoshinobu
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-10-0678
DO - 10.1158/0008-5472.CAN-10-0678
M3 - Article
C2 - 20647322
AN - SCOPUS:77955361749
VL - 70
SP - 6181
EP - 6192
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 15
ER -