title: Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation.
abstract: BACKGROUND
  End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR).
  
  
  METHODS
  222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters.
  
  
  RESULTS
  Of the 222 patients analyzed, 30 (14%) developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively) and the number of related donor kidney transplantation was significantly lower (p = 0.018) in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01) and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08). No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028). In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001).
  
  
  CONCLUSIONS
  Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR.
authors.affiliation: Department of Internal Medicine, section Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, South Holland, the Netherlands.
authors.forename: Burç
authors.initials: B
authors.lastname: Dedeoglu
authors.affiliation: Department of Internal Medicine, section Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, South Holland, the Netherlands.
authors.forename: Ruud W J
authors.initials: RW
authors.lastname: Meijers
authors.affiliation: Department of Internal Medicine, section Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, South Holland, the Netherlands.
authors.forename: Mariska
authors.initials: M
authors.lastname: Klepper
authors.affiliation: Department of Internal Medicine, section Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, South Holland, the Netherlands.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
authors.affiliation: Department of Internal Medicine, section Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, South Holland, the Netherlands.
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.affiliation: Department of Internal Medicine, section Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, South Holland, the Netherlands.
authors.forename: Nicolle H R
authors.initials: NH
authors.lastname: Litjens
authors.affiliation: Department of Internal Medicine, section Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, South Holland, the Netherlands.
authors.forename: Michiel G H
authors.initials: MG
authors.lastname: Betjes
mesh_terms: D000328:Adult; D000367:Age Factors; D018106:CD28 Antigens / Q000172:deficiency* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D016922:Cellular Senescence; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012306:Risk; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D016615:Telomere / Q000235:genetics; D013950:Thymus Gland / Q000276:immunology
chemical_list: D018106:CD28 Antigens