Potential contribution of a novel tax epitope-specific CD4+ T cells to graft-versus-tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation

Yotaro Tamai, Atsuhiko Hasegawa, Ayako Takamori, Amane Sasada, Ryuji Tanosaki, Ilseung Choi, Atae Utsunomiya, Yasuhiro Maeda, Yoshihisa Yamano, Tetsuya Eto, Ki Ryang Koh, Hirohisa Nakamae, Youko Suehiro, Koji Kato, Shigeki Takemoto, Jun Okamura, Naokuni Uike, Mari Kannagi

研究成果: Article

10 引用 (Scopus)

抄録

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATL) caused by human T cell leukemia virus type1 (HTLV-1). We previously reported that Tax-specific CD8+ cytotoxic T lymphocyte (CTL) contributed to graft-versus-ATL effects in ATL patients after allo-HSCT. However, the role of HTLV-1-specific CD4+ T cells in the effects remains unclear. In this study, we showed that Tax-specific CD4+ as well as CD8+ T cell responses were induced in some ATL patients following allo-HSCT. To further analyze HTLV-1-specific CD4+ T cell responses, we identified a novel HLA-DRB1*0101- restricted epitope, Tax155-167, recognized by HTLV-1-specific CD4+ Th1-like cells, a major population of HTLV-1-specific CD4+ T cell line, which was established from an ATL patient at 180 d after allo-HSCT from an unrelated seronegative donor by in vitro stimulation with HTLV-1-infected cells from the same patient. Costimulation of PBMCs with both the identified epitope (Tax155-167) and known CTL epitope peptides markedly enhanced the expansion of Tax-specific CD8 + T cells in PBMCs compared with stimulation with CTL epitope peptide alone in all three HLA-DRB1*0101+ patients post-allo-HSCT tested. In addition, direct detection using newly generated HLA-DRB1*0101/Tax155-167 tetramers revealed that Tax155-167-specific CD4+ T cells were present in all HTLV-1- infected individuals tested, regardless of HSCT. These results suggest that Tax155-167 may be the dominant epitope recognized by HTLV-1-specific CD4+ T cells in HLA-DRB1*0101+-infected individuals and that Tax-specific CD4+ T cells may augment the graft-versus-Tax effects via efficient induction of Tax-specific CD8+ T cell responses.

元の言語English
ページ(範囲)4382-4392
ページ数11
ジャーナルJournal of Immunology
190
発行部数8
DOI
出版物ステータスPublished - 2013 4 15
外部発表Yes

Fingerprint

Adult T Cell Leukemia Lymphoma
Deltaretrovirus
Hematopoietic Stem Cell Transplantation
Epitopes
T-Lymphocytes
Transplants
HLA-DRB1 Chains
Cytotoxic T-Lymphocytes
T-Lymphocyte Epitopes
Unrelated Donors
Peptides
Th1 Cells
Cell Line

ASJC Scopus subject areas

  • Immunology

これを引用

Potential contribution of a novel tax epitope-specific CD4+ T cells to graft-versus-tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation. / Tamai, Yotaro; Hasegawa, Atsuhiko; Takamori, Ayako; Sasada, Amane; Tanosaki, Ryuji; Choi, Ilseung; Utsunomiya, Atae; Maeda, Yasuhiro; Yamano, Yoshihisa; Eto, Tetsuya; Koh, Ki Ryang; Nakamae, Hirohisa; Suehiro, Youko; Kato, Koji; Takemoto, Shigeki; Okamura, Jun; Uike, Naokuni; Kannagi, Mari.

:: Journal of Immunology, 巻 190, 番号 8, 15.04.2013, p. 4382-4392.

研究成果: Article

Tamai, Y, Hasegawa, A, Takamori, A, Sasada, A, Tanosaki, R, Choi, I, Utsunomiya, A, Maeda, Y, Yamano, Y, Eto, T, Koh, KR, Nakamae, H, Suehiro, Y, Kato, K, Takemoto, S, Okamura, J, Uike, N & Kannagi, M 2013, 'Potential contribution of a novel tax epitope-specific CD4+ T cells to graft-versus-tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation', Journal of Immunology, 巻. 190, 番号 8, pp. 4382-4392. https://doi.org/10.4049/jimmunol.1202971
Tamai, Yotaro ; Hasegawa, Atsuhiko ; Takamori, Ayako ; Sasada, Amane ; Tanosaki, Ryuji ; Choi, Ilseung ; Utsunomiya, Atae ; Maeda, Yasuhiro ; Yamano, Yoshihisa ; Eto, Tetsuya ; Koh, Ki Ryang ; Nakamae, Hirohisa ; Suehiro, Youko ; Kato, Koji ; Takemoto, Shigeki ; Okamura, Jun ; Uike, Naokuni ; Kannagi, Mari. / Potential contribution of a novel tax epitope-specific CD4+ T cells to graft-versus-tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation. :: Journal of Immunology. 2013 ; 巻 190, 番号 8. pp. 4382-4392.
@article{a47e205e9d4a47719b4994e9b7e30e00,
title = "Potential contribution of a novel tax epitope-specific CD4+ T cells to graft-versus-tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation",
abstract = "Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATL) caused by human T cell leukemia virus type1 (HTLV-1). We previously reported that Tax-specific CD8+ cytotoxic T lymphocyte (CTL) contributed to graft-versus-ATL effects in ATL patients after allo-HSCT. However, the role of HTLV-1-specific CD4+ T cells in the effects remains unclear. In this study, we showed that Tax-specific CD4+ as well as CD8+ T cell responses were induced in some ATL patients following allo-HSCT. To further analyze HTLV-1-specific CD4+ T cell responses, we identified a novel HLA-DRB1*0101- restricted epitope, Tax155-167, recognized by HTLV-1-specific CD4+ Th1-like cells, a major population of HTLV-1-specific CD4+ T cell line, which was established from an ATL patient at 180 d after allo-HSCT from an unrelated seronegative donor by in vitro stimulation with HTLV-1-infected cells from the same patient. Costimulation of PBMCs with both the identified epitope (Tax155-167) and known CTL epitope peptides markedly enhanced the expansion of Tax-specific CD8 + T cells in PBMCs compared with stimulation with CTL epitope peptide alone in all three HLA-DRB1*0101+ patients post-allo-HSCT tested. In addition, direct detection using newly generated HLA-DRB1*0101/Tax155-167 tetramers revealed that Tax155-167-specific CD4+ T cells were present in all HTLV-1- infected individuals tested, regardless of HSCT. These results suggest that Tax155-167 may be the dominant epitope recognized by HTLV-1-specific CD4+ T cells in HLA-DRB1*0101+-infected individuals and that Tax-specific CD4+ T cells may augment the graft-versus-Tax effects via efficient induction of Tax-specific CD8+ T cell responses.",
author = "Yotaro Tamai and Atsuhiko Hasegawa and Ayako Takamori and Amane Sasada and Ryuji Tanosaki and Ilseung Choi and Atae Utsunomiya and Yasuhiro Maeda and Yoshihisa Yamano and Tetsuya Eto and Koh, {Ki Ryang} and Hirohisa Nakamae and Youko Suehiro and Koji Kato and Shigeki Takemoto and Jun Okamura and Naokuni Uike and Mari Kannagi",
year = "2013",
month = "4",
day = "15",
doi = "10.4049/jimmunol.1202971",
language = "English",
volume = "190",
pages = "4382--4392",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Potential contribution of a novel tax epitope-specific CD4+ T cells to graft-versus-tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation

AU - Tamai, Yotaro

AU - Hasegawa, Atsuhiko

AU - Takamori, Ayako

AU - Sasada, Amane

AU - Tanosaki, Ryuji

AU - Choi, Ilseung

AU - Utsunomiya, Atae

AU - Maeda, Yasuhiro

AU - Yamano, Yoshihisa

AU - Eto, Tetsuya

AU - Koh, Ki Ryang

AU - Nakamae, Hirohisa

AU - Suehiro, Youko

AU - Kato, Koji

AU - Takemoto, Shigeki

AU - Okamura, Jun

AU - Uike, Naokuni

AU - Kannagi, Mari

PY - 2013/4/15

Y1 - 2013/4/15

N2 - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATL) caused by human T cell leukemia virus type1 (HTLV-1). We previously reported that Tax-specific CD8+ cytotoxic T lymphocyte (CTL) contributed to graft-versus-ATL effects in ATL patients after allo-HSCT. However, the role of HTLV-1-specific CD4+ T cells in the effects remains unclear. In this study, we showed that Tax-specific CD4+ as well as CD8+ T cell responses were induced in some ATL patients following allo-HSCT. To further analyze HTLV-1-specific CD4+ T cell responses, we identified a novel HLA-DRB1*0101- restricted epitope, Tax155-167, recognized by HTLV-1-specific CD4+ Th1-like cells, a major population of HTLV-1-specific CD4+ T cell line, which was established from an ATL patient at 180 d after allo-HSCT from an unrelated seronegative donor by in vitro stimulation with HTLV-1-infected cells from the same patient. Costimulation of PBMCs with both the identified epitope (Tax155-167) and known CTL epitope peptides markedly enhanced the expansion of Tax-specific CD8 + T cells in PBMCs compared with stimulation with CTL epitope peptide alone in all three HLA-DRB1*0101+ patients post-allo-HSCT tested. In addition, direct detection using newly generated HLA-DRB1*0101/Tax155-167 tetramers revealed that Tax155-167-specific CD4+ T cells were present in all HTLV-1- infected individuals tested, regardless of HSCT. These results suggest that Tax155-167 may be the dominant epitope recognized by HTLV-1-specific CD4+ T cells in HLA-DRB1*0101+-infected individuals and that Tax-specific CD4+ T cells may augment the graft-versus-Tax effects via efficient induction of Tax-specific CD8+ T cell responses.

AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATL) caused by human T cell leukemia virus type1 (HTLV-1). We previously reported that Tax-specific CD8+ cytotoxic T lymphocyte (CTL) contributed to graft-versus-ATL effects in ATL patients after allo-HSCT. However, the role of HTLV-1-specific CD4+ T cells in the effects remains unclear. In this study, we showed that Tax-specific CD4+ as well as CD8+ T cell responses were induced in some ATL patients following allo-HSCT. To further analyze HTLV-1-specific CD4+ T cell responses, we identified a novel HLA-DRB1*0101- restricted epitope, Tax155-167, recognized by HTLV-1-specific CD4+ Th1-like cells, a major population of HTLV-1-specific CD4+ T cell line, which was established from an ATL patient at 180 d after allo-HSCT from an unrelated seronegative donor by in vitro stimulation with HTLV-1-infected cells from the same patient. Costimulation of PBMCs with both the identified epitope (Tax155-167) and known CTL epitope peptides markedly enhanced the expansion of Tax-specific CD8 + T cells in PBMCs compared with stimulation with CTL epitope peptide alone in all three HLA-DRB1*0101+ patients post-allo-HSCT tested. In addition, direct detection using newly generated HLA-DRB1*0101/Tax155-167 tetramers revealed that Tax155-167-specific CD4+ T cells were present in all HTLV-1- infected individuals tested, regardless of HSCT. These results suggest that Tax155-167 may be the dominant epitope recognized by HTLV-1-specific CD4+ T cells in HLA-DRB1*0101+-infected individuals and that Tax-specific CD4+ T cells may augment the graft-versus-Tax effects via efficient induction of Tax-specific CD8+ T cell responses.

UR - http://www.scopus.com/inward/record.url?scp=84875992313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875992313&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1202971

DO - 10.4049/jimmunol.1202971

M3 - Article

C2 - 23475215

AN - SCOPUS:84875992313

VL - 190

SP - 4382

EP - 4392

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -