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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 type 1 (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.
AuthorsYotaro 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
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 190 Issue 8 Pg. 4382-92 (Apr 15 2013) ISSN: 1550-6606 [Electronic] United States
PMID23475215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Epitopes, T-Lymphocyte
  • Gene Products, tax
  • tax protein, Human T-lymphotrophic virus 1
Topics
  • Aged
  • CD4-Positive T-Lymphocytes (immunology, metabolism, transplantation)
  • Epitopes, T-Lymphocyte (immunology)
  • Female
  • Gene Products, tax (administration & dosage, immunology)
  • Graft vs Leukemia Effect (immunology)
  • Hematopoietic Stem Cell Transplantation (methods)
  • Human T-lymphotropic virus 1 (immunology)
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell (immunology, surgery)
  • Male
  • Middle Aged
  • Transplantation, Homologous

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