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.
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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 -