Pathogen-specific Treg cells expand early during mycobacterium tuberculosis infection but are later eliminated in response to Interleukin-12.
Pathogen-specific Treg cells expand early during mycobacterium tuberculosis infection but are later eliminated in response to Interleukin-12.
复制标题
病原体特异性的Treg细胞在结核分枝杆菌感染期间早期膨胀，但随后因白介素12而被消除。
DOI：
10.1016/j.immuni.2013.06.003
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发表时间：
2013-06-27
期刊：
影响因子：
32.4
通讯作者：
Urdahl KB
中科院分区：
文献类型：
--
作者：
Shafiani S;Dinh C;Ertelt JM;Moguche AO;Siddiqui I;Smigiel KS;Sharma P;Campbell DJ;Way SS;Urdahl KB
胸腺衍生的Foxp 3+调节性T（Treg）细胞具有识别自身肽：MHC复合物的倾向，但它们在感染性攻击期间对表位定义的外来抗原应答的能力尚未得到证实。在这里，我们表明，肺结核分枝杆菌（Mtb），而不是李斯特菌（Lm）的感染，诱导强大的淋巴结扩增的高度活化的群体病原体特异性Treg细胞从预先存在的池胸腺来源的Treg细胞。这些抗原特异性Treg细胞在感染后3周数量达到峰值，但随后进行选择性消除，部分原因是白细胞介素-12诱导的Th 1细胞促进转录因子T-bet的内在表达。因此，最初的结核分枝杆菌诱导的炎症反应促进病原体特异性Treg细胞增殖，但这些细胞后来被积极剔除，可能是为了防止感染后期的抑制。这些发现对于预防和治疗结核病和其他慢性疾病具有重要意义，其中抗原特异性Treg细胞限制免疫力。
Thymically derived Foxp3+ regulatory T (Treg) cells have a propensity to recognize self-peptide:MHC complexes, but their ability to respond to epitope-defined foreign antigens during infectious challenge has not been demonstrated. Here we show that pulmonary infection with Mycobacterium tuberculosis (Mtb), but not Listeria monocytogenes (Lm), induced robust lymph node expansion of a highly activated population of pathogen-specific Treg cells from the pre-existing pool of thymically derived Treg cells. These antigen-specific Treg cells peaked in numbers 3 weeks after infection but subsequently underwent selective elimination driven, in part, by interleukin-12-induced intrinsic expression of the Th1-cell-promoting transcription factor T-bet. Thus, the initial Mtb-induced inflammatory response promotes pathogen-specific Treg cell proliferation, but these cells are actively culled later, probably to prevent suppression during later stages of infection. These findings have important implications for the prevention and treatment of tuberculosis and other chronic diseases in which antigen-specific Treg cells restrict immunity.
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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：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
56.9
作者：
MULLER, U;STEINHOFF, U;AGUET, M
通讯作者：
AGUET, M
影响因子：
32.4
作者：
Moon, James J.;Chu, H. Hamlet;Jenkins, Marc K.
通讯作者：
Jenkins, Marc K.