Alterations of the immune response with increasing recipient age are associated with reduced long-term organ graft function of rat kidney allografts.
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.
Pascher
Andreas
A
Department of General Surgery, Charité-Campus Virchow, Berlin, Germany.
Reutzel-Selke
Anja
A
Jurisch
Anke
A
Bachmann
Ulrike
U
Heidenhain
Christoph
C
Nickel
Peter
P
Reinke
Petra
P
Brandt
Christine
C
Pratschke
Johann
J
Frei
Ulrich
U
Neuhaus
Peter
P
Volk
Hans-Dieter
HD
Tullius
Stefan G
SG
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
D017252:CD3 Complex; D007376:Interleukin-2; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma