Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2010 Feb 16;5(2):e9232. doi: 10.1371/journal.pone.0009232.
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 naïve old B6 mice contained significantly higher frequencies of T-cells with an effector/memory phenotype (CD4(+)CD44(high)CD62L(low)). However, in-vitro proliferation (MLR) and IFNgamma-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.
老年器官移植受者是等待名单上快速增长的患者群体。我们在野生型（WT）和转基因小鼠移植模型中检查了年龄相关的 CD4(+)T 细胞功能，并分析了老年调节性 T 细胞的抑制功能。我们发现，幼稚的老 B6 小鼠脾细胞中具有效应/记忆表型（CD4(+)CD44(high)CD62L(low)）的 T 细胞频率显著升高。然而，随着年龄的增长，体外增殖（MLR）和 IFNγ 产生（ELISPOT）明显减少。同样，老年受者的皮肤移植物排斥明显延迟，观察到的移植物浸润 CD4(+)T 细胞减少。老年 CD4(+)T 细胞表现出明显的反应能力受损，表现为增殖和激活减少。相比之下，老年同种抗原特异性 CD4(+)CD25(+)FoxP3(+)T 细胞表现出剂量依赖性的良好保留的抑制功能。接下来，我们在转基因过继转移模型中检查了 18 个月大的同种反应性 T 细胞的特征。过继转移的老年 T 细胞对抗原的增殖反应明显减少。老年受者的皮肤移植物排斥明显延迟，移植物浸润细胞减少。总之，受体年龄的增加与急性排斥反应延迟以及 CD4(+)T 细胞功能和增殖受损有关，而 CD4(+)CD25(+)FoxP3(+)T 细胞（Tregs）表现出良好的功能保留。
