title: Alterations of the immune response with increasing recipient age are associated with reduced long-term organ graft function of rat kidney allografts.
abstract: BACKGROUND
  Clinically, an increasing number of older recipients are listed for transplantation. We examined recipient age-associated alterations of the immune response and their effects on graft function.
  
  
  METHODS
  Three- and 18-month-old Lewis (LEW) rats received kidneys from 3- and 18-month-old Fischer 344 (F344) rats (1.5 mg/kg/d cyclosporine A for 10 days; n=6/group) and were observed for 180 days. In additional groups, double kidney transplantations were performed to determine the impact of nephron mass and recipient age on graft outcome.
  
  
  RESULTS
  All young recipients but only 66% of old recipients survived the observation period. Increasing recipient age resulted in a significant decrease in renal allograft function (P<0.001), more advanced morphologic evidence of chronic allograft damage (P<0.001), and greater cellular infiltration (P<0.05) and major histocompatibility complex expression (P<0.01) within grafts. Additional in vitro studies examined age-related changes in the cellular immune response by enzyme-linked immunosorbent assay, fluorescence-activated cell sorter analysis, and alloreactive enzyme-linked immunospot: splenocytes from old LEW rats produced significantly more interleukin (IL)-2 (P<0.0001), IL-4 (P<0.05), interferon (IFN)-gamma (P<0.0001), and tumor necrosis factor-alpha (P<0.05). IFN-gamma-producing memory-type T cells were significantly elevated in older rats (P<0.0001). Moreover, they revealed significantly more alloreactive T cells directed against F344 (146 +/- 64.2 and 512 +/- 277/10(6) T cells; P<0.05). Double renal allografts from young donors into old recipients confirmed an independent effect of recipient age on the acceleration of chronic graft deterioration.
  
  
  CONCLUSIONS
  The enhanced cellular immune responsiveness in elderly recipients was associated with advanced chronic graft injury. Clinically, older recipients may need a modified immunosuppression.
authors.affiliation: Department of General Surgery, Charité-Campus Virchow, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pascher
authors.forename: Anja
authors.initials: A
authors.lastname: Reutzel-Selke
authors.forename: Anke
authors.initials: A
authors.lastname: Jurisch
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bachmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Heidenhain
authors.forename: Peter
authors.initials: P
authors.lastname: Nickel
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Christine
authors.initials: C
authors.lastname: Brandt
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.forename: Ulrich
authors.initials: U
authors.lastname: Frei
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Tullius
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D017252:CD3 Complex / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D018655:Lymphocyte Count; D023421:Models, Animal; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D017252:CD3 Complex; D007376:Interleukin-2; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma