title: Distinct oligoclonal T cells are associated with graft versus host disease after stem-cell transplantation.
abstract: BACKGROUND
  In patients with hematologic malignancies who receive stem-cell transplantation, donors' T cells can recognize minor histocompatibility antigens on recipient cells and generate an objective response against the tumor. However, a major side effect of such therapy is graft-versus-host disease (GVHD). The purpose of this study was to characterize distinct T-cell clones that were frequently and exclusively involved in GVHD or graft-versus-tumor (GVT) effects.
  
  
  METHODS
  We hypothesized that distinct GVHD-associated T-cell clones can be identified during the disease progression. To test this, we conducted comparative analysis of T-cell receptor (TCR) Vβs in donor-recipient pairs of patients with GVHD versus those with GVHD-free and relapse-free survival using quantitative reverse-transcriptase polymerase chain reaction and spectratyping analyses.
  
  
  RESULTS
  We identified three sets of T-cell clones that were either frequently involved in GVHD (TCR Vβ4, 11, and 23) or GVT effect (TCR Vβ9, 16, and 20), or were increased at the time of GVHD and GVT effects in a patient-specific manner (TCR Vβ2, 3, 7, 12, 15, and 17). Spectratyping analysis showed restricted clonality of the identified TCR Vβs. Polymerase chain reaction analysis also confirmed the presence of GVHD-associated T-cell clones at the site of the disease.
  
  
  CONCLUSIONS
  These data suggest that GVHD- and GVT-associated clones can be distinguished by molecular analysis of TCR Vβ to develop targeted therapy for GVHD.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, Massey Cancer Center, Richmond, VA 23298, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Berrie
authors.forename: Maciej
authors.initials: M
authors.lastname: Kmieciak
authors.forename: Roy T
authors.initials: RT
authors.lastname: Sabo
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Roberts
authors.forename: Michael O
authors.initials: MO
authors.lastname: Idowu
authors.forename: Katherine
authors.initials: K
authors.lastname: Mallory
authors.forename: Harold M
authors.initials: HM
authors.lastname: Chung
authors.forename: John M
authors.initials: JM
authors.lastname: McCarty
authors.forename: Christian A
authors.initials: CA
authors.lastname: Borrelli
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Detwiler
authors.forename: A Latif
authors.initials: AL
authors.lastname: Kazim
authors.forename: Amir A
authors.initials: AA
authors.lastname: Toor
authors.forename: Masoud H
authors.initials: MH
authors.lastname: Manjili
mesh_terms: D000328:Adult; D000368:Aged; D004247:DNA / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D019337:Hematologic Neoplasms / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA