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

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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.

Original languageEnglish
Pages (from-to)4382-4392
Number of pages11
JournalJournal of Immunology
Volume190
Issue number8
DOIs
Publication statusPublished - 2013 Apr 15

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Tamai, Y., Hasegawa, A., Takamori, A., Sasada, A., Tanosaki, R., Choi, I., Utsunomiya, A., Maeda, Y., Yamano, Y., Eto, T., Koh, K. R., 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, 190(8), 4382-4392. https://doi.org/10.4049/jimmunol.1202971