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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.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2013 Apr 15; Vol. 190 (8), pp. 4382-92. Date of Electronic Publication: 2013 Mar 08. - Publication Year :
- 2013
-
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.
- Subjects :
- Aged
CD4-Positive T-Lymphocytes metabolism
Female
Gene Products, tax administration & dosage
Human T-lymphotropic virus 1 immunology
Humans
Leukemia-Lymphoma, Adult T-Cell surgery
Male
Middle Aged
Transplantation, Homologous
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes transplantation
Epitopes, T-Lymphocyte immunology
Gene Products, tax immunology
Graft vs Leukemia Effect immunology
Hematopoietic Stem Cell Transplantation methods
Leukemia-Lymphoma, Adult T-Cell immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 190
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 23475215
- Full Text :
- https://doi.org/10.4049/jimmunol.1202971