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 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.
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Yotaro
authors.initials: Y
authors.lastname: Tamai
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Ayako
authors.initials: A
authors.lastname: Takamori
authors.forename: Amane
authors.initials: A
authors.lastname: Sasada
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tanosaki
authors.forename: Ilseung
authors.initials: I
authors.lastname: Choi
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.forename: Ki-Ryang
authors.initials: KR
authors.lastname: Koh
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.forename: Youko
authors.initials: Y
authors.lastname: Suehiro
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.forename: Shigeki
authors.initials: S
authors.lastname: Takemoto
authors.forename: Jun
authors.initials: J
authors.lastname: Okamura
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.forename: Mari
authors.initials: M
authors.lastname: Kannagi
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D016356:Gene Products, tax / Q000008:administration & dosage / Q000276:immunology*; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous
chemical_list: D018984:Epitopes, T-Lymphocyte; D016356:Gene Products, tax; C514970:tax protein, Human T-lymphotrophic virus 1