Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden.
Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden.
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DOI：
10.1186/1423-0127-18-41
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发表时间：
2011-06-15
影响因子：
11
通讯作者：
Aspinall R
中科院分区：
文献类型：
--
作者：
Ngom PT;Solon J;Moore SE;Morgan G;Prentice AM;Aspinall R
这项研究利用了一个自然的人类实验模型，让自给自足的农民经历长期和季节性修改的食物短缺和传染病负担。存在两个季节，一个是剥夺和感染增加的季节(7-12月)，另一个是丰富和低感染的季节(1-6月)；分别称为饥饿/高感染和收获/低感染的季节。先前的分析显示，在饥饿/高感染季节出生的年轻人中，与饥饿/高感染/低感染季节出生的年轻人相比，与传染病相关的死亡率高出10倍，并在婴儿时期减少胸腺输出和T细胞计数。在这里，我们报告了关于早期生活应激源作为晚年T细胞免疫缺陷发病因素的研究结果。我们假设出生季节对胸腺功能和T细胞免疫的影响在年轻人中是可以检测到的，因为Kaplan-Meier生存曲线表明这是死亡率差异最大的时期。对60例18~23岁男性(18~23岁)在饥饿/高感染和收获/低感染状态下进行T细胞亚群分析、TCRVβ谱分析和端粒长度分析。淋巴细胞总数正常且不受出生季节的影响。在饥饿/高感染季节出生的人CD3+和CD4+细胞数较低，但CD8+细胞数不是较低。CD8+端粒长度也有变短的趋势。总体而言，CD8+TCRVβ谱带偏斜，在TCRVβ12/22和TCRVβ24中分别有公开表达和缺失，但出生季节没有明显影响。我们的结论是，尽管胸腺功能没有变化，但CD4+和CD3+计数以及CD8+端粒长度的结果表明，成人T细胞免疫的某些方面受到早期生活应激源的影响。巨细胞病毒和乙肝病毒的地方性提示，慢性感染可能通过T细胞谱系的发展来调节免疫。总的影响是，这一人群过早免疫衰老的风险增加，可能是由营养和感染负担共同驱动的。
The study exploits a natural human experimental model of subsistence farmers experiencing chronic and seasonally modified food shortages and infectious burden. Two seasons existed, one of increased deprivation and infections (Jul-Dec), another of abundance and low infections (Jan-Jun); referred to as the hungry/high infection and harvest/low infection seasons respectively. Prior analysis showed a 10-fold excess in infectious disease associated mortality in young adults born in the hungry/high infection versus harvest/low infection season, and reduced thymic output and T cell counts in infancy. Here we report findings on the role of early life stressors as contributors to the onset of T cell immunological defects in later life. We hypothesised that season of birth effects on thymic function and T cell immunity would be detectable in young adults since Kaplan-Meier survival curves indicated this to be the time of greatest mortality divergence. T cell subset analyses by flow-cytometry, sjTRECs, TCRVβ repertoire and telomere length by PCR, were performed on samples from 60 males (18-23 y) selected to represent births in the hungry/high infection and harvest/low infection Total lymphocyte counts were normal and did not differ by birth season. CD3+ and CD4+ but not CD8+ counts were lower for those born during the hungry/high infection season. CD8+ telomere length also tended to be shorter. Overall, CD8+ TCRVβ repertoire skewing was observed with 'public' expressions and deletions seen in TCRVβ12/22 and TCRVβ24, respectively but no apparent effect of birth season. We conclude that, although thymic function was unchanged, the CD4+ and CD3+ counts, and CD8+ telomere length results suggested that aspects of adult T cell immunity were under the influence of early life stressors. The endemicity of CMV and HBV suggested that chronic infections may modulate immunity through T cell repertoire development. The overall implications being that, this population is at an elevated risk of premature immunosenescence possibly driven by a combination of nutritional and infectious burden.
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影响因子：
3
作者：
Fillol F;Sarr JB;Boulanger D;Cisse B;Sokhna C;Riveau G;Simondon KB;Remoué F
通讯作者：
Remoué F
DOI：
10.1084/jem.20001021
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blattman JN;Antia R;Sourdive DJ;Wang X;Kaech SM;Murali-Krishna K;Altman JD;Ahmed R
通讯作者：
Ahmed R
DOI：
10.1016/0923-2494(96)80240-9
发表时间：
1995-02-01
期刊：
RESEARCH IN IMMUNOLOGY
影响因子：
--
作者：
EVEN, J;LIM, A;KOURILSKY, P
通讯作者：
KOURILSKY, P
影响因子：
3.8
作者：
Aaby, P;Marx, C;Lisse, I
通讯作者：
Lisse, I
DOI：
10.1098/rstb.2000.0580
发表时间：
2000-03-29
影响因子：
6.3
作者：
Beverley, PCL;Maini, MK
通讯作者：
Maini, MK