At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the CD4+CD25+ T-cell fraction.
At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the CD4+CD25+ T-cell fraction.
复制标题
在CD4+ CD25+ T细胞分数中，处于风险和最近发作的1型糖尿病患者的凋亡增加。
DOI：
10.1371/journal.pone.0000146
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发表时间：
2007-01-03
期刊：
影响因子：
3.7
通讯作者：
Ghosh, Soumitra
中科院分区：
文献类型：
--
作者：
Glisic-Milosavljevic, Sanja;Waukau, Jill;Jailwala, Parthav;Jana, Srikanta;Khoo, Huoy-Jii;Albertz, Hope;Woodliff, Jeffrey;Koppen, Marilyn;Alemzadeh, Ramin;Hagopian, William;Ghosh, Soumitra
在实验模型中，通过过继转移CD4+CD25+FoxP3+抑制性或调节性T细胞可以预防1型糖尿病T1D。最近的研究发现人类疾病中存在CD4+CD25+高T细胞抑制缺陷。在这项研究中，我们测量了CD4+CD25+高T细胞的凋亡，以确定它是否有助于降低这些细胞的抑制活性。对儿童和青少年35名女性/40名男性受试者的T细胞凋亡进行了评估，受试者包括最近发病和长期患有T1D的受试者及其一级亲属，他们患T1D的风险各不相同。用YOPRO1/7AAD和细胞内caspase3活性形式染色检测细胞凋亡。分离的CD_4+CD_(25+)高和CD_4+CD_(25)−T细胞在抑制实验中共培养，以评估前者的功能。我们发现，与对照组和长期T1D受试者相比，最近发病的T1D受试者显示出CD_4+CD_(25+)高T细胞的凋亡率增加，两组均为P<；0.0001。患T1D2-3AB+Ve的高危人群分别表现出类似的趋势，p<；0.02和p<；0.01。相反，在长期存在的T1D和T2D患者中，CD_4+CD_(25+)高T细胞凋亡率与对照组p = NS处于同一水平。Caspase3和FoxP3活性形式的同时细胞内染色证实，在对照组0.002中，新近发病的FoxP3+ve CD4+CD25+高T细胞致力于凋亡的百分比高于FoxP3+ve CD4+CD25+高T细胞6.1±1.7p；0.002。与对照组相比，新发T1D患者和高危患者CD_4+CD_(25+)+高T细胞功能分别显著降低p = 0.0007和p = 0.007。在新近发病的T1D受试者和疾病高危受试者中，CD4+CD25+高T细胞中有更高水平的持续凋亡。这种高水平的CD4+CD25+高T细胞凋亡可能是导致新近发病的T1D患者这些细胞的抑制潜力显著降低的一个因素。
In experimental models, Type 1 diabetes T1D can be prevented by adoptive transfer of CD4+CD25+ FoxP3+ suppressor or regulatory T cells. Recent studies have found a suppression defect of CD4+CD25+high T cells in human disease. In this study we measure apoptosis of CD4+CD25+high T cells to see if it could contribute to reduced suppressive activity of these cells. T-cell apoptosis was evaluated in children and adolescent 35 females/40 males subjects comprising recent-onset and long-standing T1D subjects and their first-degree relatives, who are at variable risk to develop T1D. YOPRO1/7AAD and intracellular staining of the active form of caspase 3 were used to evaluate apoptosis. Isolated CD4+CD25+high and CD4+CD25− T cells were co-cultured in a suppression assay to assess the function of the former cells. We found that recent-onset T1D subjects show increased apoptosis of CD4+CD25+high T cells when compared to both control and long-standing T1D subjects p<0.0001 for both groups. Subjects at high risk for developing T1D 2–3Ab+ve show a similar trend p<0.02 and p<0.01, respectively. On the contrary, in long-standing T1D and T2D subjects, CD4+CD25+high T cell apoptosis is at the same level as in control subjects p = NS. Simultaneous intracellular staining of the active form of caspase 3 and FoxP3 confirmed recent-onset FoxP3+ve CD4+CD25+high T cells committed to apoptosis at a higher percentage 15.3±2.2 compared to FoxP3+ve CD4+CD25+high T cells in control subjects 6.1±1.7 p<0.002. Compared to control subjects, both recent-onset T1D and high at-risk subjects had significantly decreased function of CD4+CD25+high T cells p = 0.0007 and p = 0.007, respectively. There is a higher level of ongoing apoptosis in CD4+CD25+high T cells in recent-onset T1D subjects and in subjects at high risk for the disease. This high level of CD4+CD25+high T-cell apoptosis could be a contributing factor to markedly decreased suppressive potential of these cells in recent-onset T1D subjects.
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CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.3
作者：
Fahlén, L;Read, S;Gorelik, L;Hurst, SD;Coffman, RL;Flavell, RA;Powrie, F
通讯作者：
Powrie, F
影响因子：
4.6
作者：
Gregg, R;Smith, CM;Moss, PA
通讯作者：
Moss, PA
影响因子：
4.4
作者：
Baecher-Allan, C;Viglietta, V;Hafler, DA
通讯作者：
Hafler, DA
影响因子：
7.7
作者：
Brusko, TM;Wasserfall, CH;Atkinson, MA
通讯作者：
Atkinson, MA