T cell receptor CDR3 sequence but not recognition characteristics distinguish autoreactive effector and Foxp3(+) regulatory T cells.
T cell receptor CDR3 sequence but not recognition characteristics distinguish autoreactive effector and Foxp3(+) regulatory T cells.
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DOI：
10.1016/j.immuni.2009.09.023
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发表时间：
2009-12-18
期刊：
影响因子：
32.4
通讯作者：
Geiger TL
中科院分区：
文献类型：
--
作者：
Liu X;Nguyen P;Liu W;Cheng C;Steeves M;Obenauer JC;Ma J;Geiger TL
叉头框转录因子3（Foxp3）+调节性T（Treg）和常规T（Tconv）细胞群在自身免疫病理学部位的来源，特异性和可塑性尚未得到很好的表征。为了评估这一点，我们结合了整体的剧目分析和功能评估分离的T细胞受体（TCR）的TCRα逆转录小鼠与自身免疫性脑脊髓炎。Treg和Tconv细胞TCR库是不同的，并且自身抗原特异性Treg和Tconv细胞在患病组织中富集。这些细胞的自身抗原敏感性和精细的特异性，这意味着反应性的差异不负责谱系规范。值得注意的是，自身反应性Treg和Tconv细胞可以通过单个TCR CDR 3残基处的酸性相对于脂肪族变异来完全区分。我们的研究结果表明，个体发育不同的Treg和Tconv细胞库与收敛特异性的自身抗原在自身免疫反应过程中，反对超过有限的可塑性Treg和Tconv细胞在自身免疫炎症。
The source, specificity, and plasticity of the forkhead box transcription factor 3 (Foxp3)+ regulatory T (Treg) and conventional T (Tconv) cell populations active at sites of autoimmune pathology are not well characterized. To evaluate this, we combined global repertoire analyses and functional assessments of isolated T cell receptors (TCR) from TCRα retrogenic mice with autoimmune encephalomyelitis. Treg and Tconv cell TCR repertoires were distinct, and autoantigen-specific Treg and Tconv cells were enriched in diseased tissue. Autoantigen sensitivity and fine specificity of these cells intersected, implying that differences in responsiveness were not responsible for lineage specification. Notably, autoreactive Treg and Tconv cells could be fully distinguished by an acidic versus aliphatic variation at a single TCR CDR3 residue. Our results imply that ontogenically distinct Treg and Tconv cell repertoires with convergent specificities for autoantigen respond during autoimmunity and argue against more than limited plasticity between Treg and Tconv cells during autoimmune inflammation.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
通讯作者：
Rudensky, AY
DOI：
10.1084/jem.20081359
发表时间：
2008-12-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lathrop SK;Santacruz NA;Pham D;Luo J;Hsieh CS
通讯作者：
Hsieh CS
影响因子：
82.9
作者：
Korn, Thomas;Reddy, Jayagopala;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
4.4
作者：
McGeachy, MJ;Stephens, LA;Anderton, SM
通讯作者：
Anderton, SM