Modified CD4(+)  T-cell response in recipients of old cardiac allografts.
With an increasing demand, organs from elderly donors are more frequently utilized for transplantation. Herein, we analyzed the impact of donor age on CD4(+) T-cell responses with regard to regulatory and effector mechanisms. Young (3months) BM12 recipients were engrafted with young or old (18months) B6 cardiac allografts. Systemic CD4(+) T-cell responses and intragraft changes were monitored and compared to age-matched syngenic transplant controls. While elderly, nonmanipulated hearts contained significantly elevated frequencies of donor-derived leukocytes prior to transplantation, allograft survival was age-independent. T-cell activation, however, was delayed and associated with a compromised immune response in mixed lymphocyte cultures (MLR; P=0.0002) early after transplantation (day 14). During the time course after transplantation, recipients of old grafts demonstrated an augmented immune response as shown by significantly higher frequencies of activated CD4(+) T-cells and a stronger in vitro alloreactivity (MLR; ELISPOT; P<0.01). In parallel, frequencies of regulatory T-cells had increased systemically and overall fewer CD4(+) T-cells were detected intragraft. Interestingly, changes in the CD4(+) T-cell response were not reflected by graft morphology. Of note, transplantation of young and old syngenic hearts did not show age-related differences of the CD4(+) T-cells response suggesting that old grafts can recover from a period of short cold ischemia time. Our data suggest that donor age is associated with an augmented CD4(+) T-cells response which did not affect graft survival in our model. These findings contribute to a better understanding of the immune response following the engraftment of older donor organs.
Transplant Surgery Research Laboratory and Division of Transplant Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Christian
C
Denecke
Xupeng
X
Ge
Anke
A
Jurisch
Sonja
S
Kleffel
Irene K
IK
Kim
Robert F
RF
Padera
Anne
A
Weiland
Paolo
P
Fiorina
Johann
J
Pratschke
Stefan G
SG
Tullius
D000367:Age Factors; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology