title: Long-term persistence of limited HTLV-I Tax-specific cytotoxic T cell clones in a patient with adult T cell leukemia/lymphoma after allogeneic stem cell transplantation.
abstract: OBJECTIVE
  Adult T cell leukemia/lymphoma (ATL) is a highly aggressive malignancy of T cells caused by human T cell lymphotropic virus type 1 (HTLV-1). Recent clinical studies have suggested that allogeneic stem cell transplantation (HSCT) improves the clinical course of ATL by harnessing a graft-versus-ATL effect, and that donor-derived HTLV-1 Tax-specific CD8(+) cytotoxic T cells (CTLs) contribute to the graft-versus-ATL effect after HSCT. However, little is known about the immunological characteristics of Tax-specific CTLs in ATL patients who underwent HSCT.
  
  
  METHODS
  We serially analyzed frequencies, differentiation, functions and clonal dynamics of Tax-specific CTLs in paired samples of peripheral blood (PB) and bone marrow (BM) from an ATL patient after HSCT at the single-cell level. We used flowcytometric and single-cell T cell receptor (TCR) repertoire analysis methods without culture steps.
  
  
  RESULTS
  Donor-derived Tax-specific CTLs effectively suppressed HTLV-1 replication in both PB and BM at least during chronic graft-versus-host disease after HSCT. Furthermore, Tax-specific CTLs had comparable properties between BM and PB, except for preferential accumulation in BM rather than PB. Tax-specific CTLs persistently existed as less-differentiated CD45RA(-)CCR7(-) effector memory CTLs based on predominant phenotypes of CD27(+), CD28(+/-) and CD57(+/-). Our approach using single-cell TCR repertoire analysis method showed highly restricted oligoclonal responses of Tax-specific CTLs, and TCR BV7- or BV30- expressing two predominant CTL clones persistently existed and maintained strong cytotoxic activities against HTLV-1 in both PB and BM over three years after HSCT.
  
  
  CONCLUSIONS
  These findings about Tax-specific CTLs provide insights into future directions for studies on immunotherapy against ATL.
authors: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya-ku, Saitama, Saitama, 330-8503, Japan.
authors: Yukie
authors: Y
authors: Tanaka
authors: Hideki
authors: H
authors: Nakasone
authors: Rie
authors: R
authors: Yamazaki
authors: Hidenori
authors: H
authors: Wada
authors: Yuko
authors: Y
authors: Ishihara
authors: Koji
authors: K
authors: Kawamura
authors: Kana
authors: K
authors: Sakamoto
authors: Masahiro
authors: M
authors: Ashizawa
authors: Tomohito
authors: T
authors: Machishima
authors: Miki
authors: M
authors: Sato
authors: Kiriko
authors: K
authors: Terasako
authors: Shun-ichi
authors: S
authors: Kimura
authors: Misato
authors: M
authors: Kikuchi
authors: Shinya
authors: S
authors: Okuda
authors: Shinichi
authors: S
authors: Kako
authors: Junya
authors: J
authors: Kanda
authors: Aki
authors: A
authors: Tanihara
authors: Junji
authors: J
authors: Nishida
authors: Yoshinobu
authors: Y
authors: Kanda
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002999:Clone Cells; D016356:Gene Products, tax / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D020544:Graft vs Leukemia Effect; D015490:HTLV-I Infections / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D059010:Single-Cell Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D016356:Gene Products, tax