Prolonged graft survival in older recipient mice is determined by impaired effector T-cell but intact regulatory T-cell responses.
Prolonged graft survival in older recipient mice is determined by impaired effector T-cell but intact regulatory T-cell responses.
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DOI：
10.1371/journal.pone.0009232
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发表时间：
2010-02-16
期刊：
影响因子：
3.7
通讯作者：
Tullius SG
中科院分区：
文献类型：
--
作者：
Denecke C;Bedi DS;Ge X;Kim IK;Jurisch A;Weiland A;Habicht A;Li XC;Tullius SG
老年器官移植受者在等候名单上的病人中占了快速增长的比例。我们在野生型（WT）和转基因小鼠移植模型中检测了年龄依赖性CD4+ t细胞的功能，并分析了老年调节性t细胞的抑制功能。我们发现naïve老年B6小鼠的脾细胞含有具有效应/记忆表型（CD4+CD44highCD62Llow）的t细胞的频率显著更高。然而，随着年龄的增加，体外增殖（MLR）和ifn γ-产生（ELISPOT）明显降低。同样，皮肤移植排斥反应在老年受者中明显延迟，移植浸润CD4+ t细胞较少。衰老的CD4+ t细胞表现出明显的反应性受损，增殖和激活减少。相比之下，老的同种异体抗原特异性CD4+CD25+FoxP3+ t细胞表现出剂量依赖性的保存良好的抑制功能。接下来，我们在转基因过继转移模型中检测了18个月大的同种异体反应性t细胞的特征。过继性转移的老t细胞对抗原的反应明显减少。皮肤移植排斥反应在老年受者中明显延迟，移植物浸润细胞减少。综上所述，高龄受体与延迟的急性排斥反应和CD4+ t细胞功能和增殖受损有关，而CD4+CD25+FoxP3+ t细胞（Tregs）的功能保存良好。
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+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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影响因子：
4.6
作者：
Gregg, R;Smith, CM;Moss, PA
通讯作者：
Moss, PA
影响因子：
5.4
作者：
ROSENBERG, AS;SECHLER, JMG;BLOOM, ET
通讯作者：
BLOOM, ET
影响因子：
7.7
作者：
Brusko, TM;Wasserfall, CH;Atkinson, MA
通讯作者：
Atkinson, MA
影响因子：
4.4
作者：
Habicht, A;Clarkson, MR;Sayegh, MH
通讯作者：
Sayegh, MH
DOI：
10.1023/a:1008246129084
发表时间：
1997-01-01
期刊：
Geriatric nephrology and urology
影响因子：
--
作者：
Jassal, S V;Opelz, G;Cole, E
通讯作者：
Cole, E