TY - JOUR
T1 - Prolonged graft survival in older recipient mice is determined by impaired effector T-cell but intact regulatory T-cell responses
AU - Denecke, Christian
AU - Bedi, Damanpreet Singh
AU - Ge, Xupeng
AU - Kim, Irene Kyung Eun
AU - Jurisch, Anke
AU - Weiland, Anne
AU - Habicht, Antje
AU - Li, Xian C.
AU - Tullius, Stefan G.
PY - 2010/2/16
Y1 - 2010/2/16
N2 - Elderly organ transplant recipients represent a fast growing segment of patients on the waiting list. We examined age-dependent CD4+ T-cell functions in a wild-type (WT) and a transgenic mouse transplant model and analyzed the suppressive function of old regulatory T-cells. We found that splenocytes of na?̈ve old B6 mice contained significantly higher frequencies of T-cells with an effector/memory phenotype (CD4+CD44highCD62Llow). However, in-vitro proliferation (MLR) and IFNγ-production (ELISPOT) were markedly reduced with increasing age. Likewise, skin graft rejection was significantly delayed in older recipients and fewer graft infiltrating CD4 +T-cells were observed. Old CD4+ T-cells demonstrated a significant impaired responsiveness as indicated by diminished proliferation and activation. In contrast, old alloantigen-specific CD4+CD25 +FoxP3+ T-cells demonstrated a dose-dependent well-preserved suppressor function. Next, we examined characteristics of 18-month old alloreactive T-cells in a transgenic adoptive transfer model. Adoptively transferred old T-cells proliferated significantly less in response to antigen. Skin graft rejection was significantly delayed in older recipients, and graft infiltrating cells were reduced. In summary, advanced recipient age was associated with delayed acute rejection and impaired CD4+ T-cell function and proliferation while CD4+CD25+FoxP3 + T-cells (Tregs) showed a well-preserved function.
AB - Elderly organ transplant recipients represent a fast growing segment of patients on the waiting list. We examined age-dependent CD4+ T-cell functions in a wild-type (WT) and a transgenic mouse transplant model and analyzed the suppressive function of old regulatory T-cells. We found that splenocytes of na?̈ve old B6 mice contained significantly higher frequencies of T-cells with an effector/memory phenotype (CD4+CD44highCD62Llow). However, in-vitro proliferation (MLR) and IFNγ-production (ELISPOT) were markedly reduced with increasing age. Likewise, skin graft rejection was significantly delayed in older recipients and fewer graft infiltrating CD4 +T-cells were observed. Old CD4+ T-cells demonstrated a significant impaired responsiveness as indicated by diminished proliferation and activation. In contrast, old alloantigen-specific CD4+CD25 +FoxP3+ T-cells demonstrated a dose-dependent well-preserved suppressor function. Next, we examined characteristics of 18-month old alloreactive T-cells in a transgenic adoptive transfer model. Adoptively transferred old T-cells proliferated significantly less in response to antigen. Skin graft rejection was significantly delayed in older recipients, and graft infiltrating cells were reduced. In summary, advanced recipient age was associated with delayed acute rejection and impaired CD4+ T-cell function and proliferation while CD4+CD25+FoxP3 + T-cells (Tregs) showed a well-preserved function.
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U2 - 10.1371/journal.pone.0009232
DO - 10.1371/journal.pone.0009232
M3 - Article
C2 - 20169060
AN - SCOPUS:77949495502
VL - 5
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 2
M1 - e9232
ER -