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.
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Authors | 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 |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 190
Issue 8
Pg. 4382-92
(Apr 15 2013)
ISSN: 1550-6606 [Electronic] United States |
PMID | 23475215
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Epitopes, T-Lymphocyte
- Gene Products, tax
- tax protein, Human T-lymphotrophic virus 1
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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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