Graft-versus-Tax Response in Adult T-Cell Leukemia Patients after Hematopoietic Stem Cell Transplantation

Nanae Harashima, Kiyoshi Kurihara, Atae Utsunomiya, Ryuji Tanosaki, Shino Hanabuchi, Masato Masuda, Takashi Ohashi, Fumiyo Fukui, Atsuhiko Hasegawa, Takao Masuda, Yoichi Takaue, Jun Okamura, Mari Kannagi

Research output: Contribution to journalArticle

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Abstract

Adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I) is characterized by poor prognosis after chemotherapy. Recent clinical trials have indicated, however, that allogeneic but not autologous hematopoietic stem cell transplantation (HSCT) for ATL can yield better clinical outcomes. In the present study, we investigated cellular immune responses of ATL patients who obtained complete remission after nonmyeloablative allogeneic peripheral blood HSCT from HLA-identical sibling donors. In the culture of peripheral blood mononuclear cells (PBMCs) from a post-HSCT but not pre-HSCT ATL patient, CD8+ CTLs proliferated vigorously in response to stimulation with autologous HTLV-I-infected T cells that had been established before HSCT in vitro. These CTLs contained a large number of monospecific CTL population directed to a HLA-A2-restricted HTLV-I Tax 11-19 epitope. The frequency of Tax 11-19-specific CD8+ CTLs in this patient markedly increased also in vivo after HSCT, as determined by staining with HLA-A2/Tax 11-19 tetramers. Similar clonal expansion of HTLV-I Tax-specific CTLs exclusively directed to a HLA-A24-restricted Tax 301-309 epitope was observed in the PBMCs from another ATL patient after HSCT from a HTLV-I-negative donor. Among four post-HSCT ATL patients tested, HTLV-I-specific CTLs were induced in the PBMC culture from three patients but not from the remaining one who had later recurrence of ATL. These observations suggested that reconstituted immunity against antigen presentation in ATL patients after HSCT resulted in strong and selective graft-versus-HTLV-I response, which might contribute to graft-versus-leukemia effects.

Original languageEnglish
Pages (from-to)391-399
Number of pages9
JournalCancer Research
Volume64
Issue number1
DOIs
Publication statusPublished - 2004 Jan 1
Externally publishedYes

Fingerprint

Adult T Cell Leukemia Lymphoma
Hematopoietic Stem Cell Transplantation
Human T-lymphotropic virus 1
Transplants
HLA-A2 Antigen
Blood Cells
Epitopes
HLA-A24 Antigen
Tissue Donors
Peripheral Blood Stem Cell Transplantation
Antigen Presentation
Cellular Immunity
Siblings
Immunity
Leukemia
Cell Culture Techniques
Clinical Trials
Staining and Labeling
T-Lymphocytes
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Graft-versus-Tax Response in Adult T-Cell Leukemia Patients after Hematopoietic Stem Cell Transplantation. / Harashima, Nanae; Kurihara, Kiyoshi; Utsunomiya, Atae; Tanosaki, Ryuji; Hanabuchi, Shino; Masuda, Masato; Ohashi, Takashi; Fukui, Fumiyo; Hasegawa, Atsuhiko; Masuda, Takao; Takaue, Yoichi; Okamura, Jun; Kannagi, Mari.

In: Cancer Research, Vol. 64, No. 1, 01.01.2004, p. 391-399.

Research output: Contribution to journalArticle

Harashima, N, Kurihara, K, Utsunomiya, A, Tanosaki, R, Hanabuchi, S, Masuda, M, Ohashi, T, Fukui, F, Hasegawa, A, Masuda, T, Takaue, Y, Okamura, J & Kannagi, M 2004, 'Graft-versus-Tax Response in Adult T-Cell Leukemia Patients after Hematopoietic Stem Cell Transplantation', Cancer Research, vol. 64, no. 1, pp. 391-399. https://doi.org/10.1158/0008-5472.CAN-03-1452
Harashima, Nanae ; Kurihara, Kiyoshi ; Utsunomiya, Atae ; Tanosaki, Ryuji ; Hanabuchi, Shino ; Masuda, Masato ; Ohashi, Takashi ; Fukui, Fumiyo ; Hasegawa, Atsuhiko ; Masuda, Takao ; Takaue, Yoichi ; Okamura, Jun ; Kannagi, Mari. / Graft-versus-Tax Response in Adult T-Cell Leukemia Patients after Hematopoietic Stem Cell Transplantation. In: Cancer Research. 2004 ; Vol. 64, No. 1. pp. 391-399.
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abstract = "Adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I) is characterized by poor prognosis after chemotherapy. Recent clinical trials have indicated, however, that allogeneic but not autologous hematopoietic stem cell transplantation (HSCT) for ATL can yield better clinical outcomes. In the present study, we investigated cellular immune responses of ATL patients who obtained complete remission after nonmyeloablative allogeneic peripheral blood HSCT from HLA-identical sibling donors. In the culture of peripheral blood mononuclear cells (PBMCs) from a post-HSCT but not pre-HSCT ATL patient, CD8+ CTLs proliferated vigorously in response to stimulation with autologous HTLV-I-infected T cells that had been established before HSCT in vitro. These CTLs contained a large number of monospecific CTL population directed to a HLA-A2-restricted HTLV-I Tax 11-19 epitope. The frequency of Tax 11-19-specific CD8+ CTLs in this patient markedly increased also in vivo after HSCT, as determined by staining with HLA-A2/Tax 11-19 tetramers. Similar clonal expansion of HTLV-I Tax-specific CTLs exclusively directed to a HLA-A24-restricted Tax 301-309 epitope was observed in the PBMCs from another ATL patient after HSCT from a HTLV-I-negative donor. Among four post-HSCT ATL patients tested, HTLV-I-specific CTLs were induced in the PBMC culture from three patients but not from the remaining one who had later recurrence of ATL. These observations suggested that reconstituted immunity against antigen presentation in ATL patients after HSCT resulted in strong and selective graft-versus-HTLV-I response, which might contribute to graft-versus-leukemia effects.",
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