title: Clinical significance of regulatory T-cell-related gene expression in peripheral blood after renal transplantation.
abstract: BACKGROUND
  Regulatory T cells (Tregs) have been suggested to be deeply associated with immune tolerance and long-term graft survival in transplantation. Some recipients with stable graft function (ST) could possibly minimize immunosuppression during the maintenance period. However, effective assays for assessing the suitability of patients have yet to be established. The purpose of this study was to elucidate the clinical relevance of Treg-related gene expression such as forkhead box P3 (Foxp3) in peripheral blood after renal transplantation.
  
  
  METHODS
  Several key molecules related to the function of immune cells such as Treg, including Foxp3, transforming growth factor-β, cytotoxic T-lymphocyte antigen-4, chemokine receptor 7, toll-like receptor 4, granzyme B, T-bet, GATA3, RORC, α1,2-mannosidase, and proteasome subunit β 10 were examined in the peripheral blood of 272 renal transplant recipients by quantitative real-time reverse-transcriptase polymerase chain reaction. The expression levels were compared between recipients with chronic rejection and ST.
  
  
  RESULTS
  Foxp3 messenger RNA (mRNA) levels were reduced immediately after transplantation and gradually recovered. Pretransplantation levels were closely correlated with 1 year posttransplantation levels. Recipients with chronic rejection had significantly lower levels of Foxp3, chemokine receptor 7, and granzyme B mRNA, and higher levels of toll-like receptor 4 and proteasome subunit β 10 mRNA compared with those with ST, although Foxp3 was the most relevant marker.
  
  
  CONCLUSIONS
  There is a possibility that monitoring mRNA expression levels of Treg-related molecules in peripheral blood might offer useful information on patient selection and early detection of rejection when immunosuppression minimization strategy is implemented in renal transplantation.
authors.affiliation: Department of Applied Immunology, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Iwase
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miwa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kuzuya
authors.forename: Kenta
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Masataka
authors.initials: M
authors.lastname: Haneda
authors.forename: Akio
authors.initials: A
authors.lastname: Katayama
authors.forename: Asami
authors.initials: A
authors.lastname: Takeda
authors.forename: Kunio
authors.initials: K
authors.lastname: Morozumi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Watarai
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Uchida
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006084:Graft Rejection / Q000097:blood / Q000235:genetics / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology
chemical_list: D065095:Calcineurin Inhibitors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006680:HLA Antigens; D007518:Isoantibodies; D012333:RNA, Messenger