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  • Oral presentation
  • Open Access

Augmentation of donor-derived Tax-specific CTL responses by a novel Tax epitope-specific CD4+ helper T-cells in ATL patients after allogeneic hematopoietic stem cell transplantation

  • 1Email author,
  • 1,
  • 1,
  • 1,
  • 2,
  • 3,
  • 4,
  • 5,
  • 6,
  • 7,
  • 8,
  • 8,
  • 3,
  • 9,
  • 10,
  • 11,
  • 3 and
  • 1
Retrovirology201411 (Suppl 1) :O35

https://doi.org/10.1186/1742-4690-11-S1-O35

  • Published:

Keywords

  • Allogeneic Hematopoietic Stem Cell Transplantation
  • Seronegative Donor
  • Intrinsic Drug Resistance

Adult T-cell leukemia/ lymphoma (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) and characterized by extremely poor prognosis because of intrinsic drug resistance to cytotoxic agents. Recently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been shown to be an effective treatment for ATL due to graft-versus-leukemia effects. However, donor-derived HTLV-1-specific T-cell responses in ATL patients after allo-HSCT are not well understood. In this study, blood samples from 15 ATL patients at 180 days following allo-HSCT from seronegative donors were screened for IFN-g production of donor-derived T-cells against Tax protein. Among 15 patients, Tax-specific T-cell responses were observed in 11 patients. Direct detection with Tax/MHC class I tetramers revealed that donor-derived Tax-specific CD8+ cytotoxic T-lymphocytes (CTLs) were present in 12 of 15 patients. We then identified a novel Tax epitope (Tax155-167) presented by HLA-DR1 (HLA-DRB1*0101) and examined the presence of Tax-specific CD4+ T-cells in 3 HLA-DR1+ patients after allo-HSCT using a newly generated Tax155-167/HLA-DR1 tetramer. Tax155-167-specific CD4+ T-cells were found to be present in all HLA-DR1+ patients tested. Furthermore, in vitro stimulation of PBMCs from HLA-DR1+ HLA-A*2402+ patients with both Tax155-167 and HLA-A*2402-restricted CTL epitope (Tax301-309) led to robust expansion of Tax301-309-specific CTLs. Our results suggest that donor-derived HTLV-1-specific both CD4+ and CD8+ T-cells could be induced in ATL patients after allo-HSCT from seronegative donors, probably due to exposure to HTLV-1 antigens from recipient-derived ATL cells, and the HTLV-1-specific CD4+ T-cells may contribute to efficient induction of donor-derived HTLV-1-specific CTL responses.

Authors’ Affiliations

(1)
Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo, Japan
(2)
Clinical Laboratories Division, National Cancer Center Hospital, Tokyo, Japan
(3)
Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan
(4)
Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan
(5)
Division of Hematology, Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan
(6)
Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
(7)
Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
(8)
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan
(9)
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
(10)
Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
(11)
Institute for Clinical Research, National Kyushu Cancer Center, Fukuoka, Japan

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