title: Persistence of recipient-derived as well as donor-derived clones of cytomegalovirus pp65-specific cytotoxic T cells long after allogeneic hematopoietic stem cell transplantation.
abstract: BACKGROUND
  Cytomegalovirus (CMV)-specific CD8(+) cytotoxic T lymphocytes (CMV-CTLs) play a crucial role in preventing CMV disease. However, the actual in vivo dynamics of CMV-CTL clones after allogeneic hematopoietic stem cell transplantation (alloHCT) are still unclear.
  
  
  METHODS
  Using a single-cell T-cell receptor repertoire analysis, we monitored clones and chimerism of CMV-CTLs in 3 CMV-seropositive alloHCT recipients from CMV-seronegative donors, with or without CMV reactivation.
  
  
  RESULTS
  Nearly all of the CMV-CTLs during follow-up were CD45RA(-) CCR7(-) effector memory/CD45RA(+) CCR7(-) effector T cells, and were highly matured. In each case, the use of BV gene families was restricted, especially in BV5, 7, 28, and 29. Although no common predominant CMV-CTL clones were found, several shared motifs of complementarity-determining region-3 were identified among the 3 cases; QGA in all, TGE and TDT in Case 1 and Case 2, and RDRG in Case 2 and Case 3. In all cases, CMV-CTL clones that were detected for the first time after alloHCT persisted as the dominant clones. In Case 1, without CMV reactivation, recipient-derived CMV-CTLs exclusively persisted as a dominant clone, while all CMV-CTLs in the other 2 cases, with CMV reactivation, were donor derived.
  
  
  CONCLUSIONS
  Clone monitoring and chimerism analyses should help to further clarify novel aspects of immuno-reconstitution after alloHCT.
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Terasako-Saito
authors.forename: H
authors.initials: H
authors.lastname: Nakasone
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: R
authors.initials: R
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ishihara
authors.forename: K
authors.initials: K
authors.lastname: Kawamura
authors.forename: Y
authors.initials: Y
authors.lastname: Akahoshi
authors.forename: J
authors.initials: J
authors.lastname: Hayakawa
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: N
authors.initials: N
authors.lastname: Harada
authors.forename: H
authors.initials: H
authors.lastname: Nakano
authors.forename: K
authors.initials: K
authors.lastname: Kameda
authors.forename: T
authors.initials: T
authors.lastname: Ugai
authors.forename: R
authors.initials: R
authors.lastname: Yamasaki
authors.forename: M
authors.initials: M
authors.lastname: Ashizawa
authors.forename: S-I
authors.initials: SI
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: A
authors.initials: A
authors.lastname: Tanihara
authors.forename: J
authors.initials: J
authors.lastname: Kanda
authors.forename: S
authors.initials: S
authors.lastname: Kako
authors.forename: J
authors.initials: J
authors.lastname: Nishida
authors.forename: Y
authors.initials: Y
authors.lastname: Kanda
mesh_terms: D003587:Cytomegalovirus; D005260:Female; D005786:Gene Expression Regulation; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism; D059871:HLA-A24 Antigen / Q000235:genetics / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014019:Tissue Donors; D014763:Viral Matrix Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: C438506:HLA-A*24:02 antigen; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D007166:Immunosuppressive Agents; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa
keywords: CMV; CTL; HLA-A*2402-restricted cytomegalovirus-specific cytotoxic T cells; T cell receptor-β; chimerism analysis; clone monitoring; single-cell analysis