title: Grafts from elderly donors elicit a stronger immune response in the early period posttransplantation: a study in a rat model.
abstract: With a growing demand for transplants, grafts from older donors are increasingly used. However, altered immune responses associated with increasing donor age may influence graft survival. We dissected the effects of donor age on the immune response in an experimental model. Kidneys from young and old F-344 donors (3 and 18 months) transplanted into young Lewis recipients (3 months) were followed for 6 months. Renal function, structural changes, and immune activation were tested at serial time intervals. Splenocytes and peripheral blood mononuclear cells were examined by flow cytometry; alloantigen-specific intracellular IFN-gamma secretion was evaluated by ELISPOT. Grafts from both young and old donors survived the observation period. The ratio of structural changes (6/1 months) increased twofold in old vs young grafts. In parallel, the ratio of renal function declined by fivefold in recipients of old donor kidneys. Most interestingly, elderly grafts produced a modified immune response: the numbers of T/B cells and alloreactive T cells increased early following the transplantation of old grafts (P < .05). However, by 6 months, the amounts of T and B cells as well as alloantigen-specific immune responses were comparable in recipients of old versus young grafts. Older grafts elicit a stronger immune response during the early period posttransplantation. This process is associated with an increased immunogenicity in older grafts. Clinical immunosuppressive protocols need to consider these effects.
authors.affiliation: Department of General and Transplantation Surgery, University of Medicine Berlin, Charité, Virchow Clinic, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Reutzel-Selke
authors.forename: A
authors.initials: A
authors.lastname: Filatenkov
authors.forename: A
authors.initials: A
authors.lastname: Jurisch
authors.forename: C
authors.initials: C
authors.lastname: Denecke
authors.forename: P N A
authors.initials: PN
authors.lastname: Martins
authors.forename: A
authors.initials: A
authors.lastname: Pascher
authors.forename: S
authors.initials: S
authors.lastname: Jonas
authors.forename: J
authors.initials: J
authors.lastname: Pratschke
authors.forename: P
authors.initials: P
authors.lastname: Neuhaus
authors.forename: S G
authors.initials: SG
authors.lastname: Tullius
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006085:Graft Survival / Q000502:physiology*; D016030:Kidney Transplantation / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous / Q000276:immunology