Interferons Direct Th2 Cell Reprogramming to Generate a Stable GATA-3+T-bet+ Cell Subset with Combined Th2 and Th1 Cell Functions
Interferons Direct Th2 Cell Reprogramming to Generate a Stable GATA-3+T-bet+ Cell Subset with Combined Th2 and Th1 Cell Functions
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DOI：
10.1016/j.immuni.2009.12.004
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发表时间：
2010-01-29
期刊：
影响因子：
32.4
通讯作者：
Loehning, Max
中科院分区：
文献类型：
--
作者：
Hegazy, Ahmed N.;Peine, Michael;Loehning, Max
当前的T细胞分化模型调用了由谱系指定转录因子GATA-3和T-BET控制的单独的T辅助2（TH2）和Th1细胞谱系。但是，关于Th2细胞谱系承诺可塑性的知识是有限的。在这里，我们表明，促进Th1细胞促进淋巴细胞绒毛膜炎病毒（LCMV）对感染进行了重新编程，否则稳定地承诺的GATA-3（+）Th2细胞采用了GATA-3（+）T-bet（+）（+）和interleuukin-4（+）在体内维持几个月的干扰素伽马（+）“ Th2+1”表型。 Th2细胞重编程需要T细胞受体刺激，I型和11型干扰素和白介素12信号以及T-BET。在收养的病毒特异性Th2细胞中，LCMV触发的T-BET诱导对于防止病毒持久性和致命的免疫病理学至关重要。因此，不利分化的Th2细胞的功能重编程可能有助于建立保护性免疫反应。 GATA-3和T-BET的稳定共表达为单个记忆T细胞中Th2和Th1细胞谱系特征的长期共存提供了一个分子概念。
Current T cell differentiation models invoke separate T helper 2 (Th2) and Th1 cell lineages governed by the lineage-specifying transcription factors GATA-3 and T-bet. However, knowledge on the plasticity of Th2 cell lineage commitment is limited. Here we show that infection with Th1 cell-promoting lymphocytic choriomeningitis virus (LCMV) reprogrammed otherwise stably committed GATA-3(+) Th2 cells to adopt a GATA-3(+)T-bet(+) and interleukin-4(+)interferon-gamma(+) "Th2+1" phenotype that was maintained in vivo for months. Th2 cell reprogramming required T cell receptor stimulation, concerted type I and type 11 interferon and interleukin-12 signals, and T-bet. LCMV-triggered T-bet induction in adoptively transferred virus-specific Th2 cells was crucial to prevent viral persistence and fatal immunopathology. Thus, functional reprogramming of unfavorably differentiated Th2 cells may facilitate the establishment of protective immune responses. Stable coexpression of GATA-3 and T-bet provides a molecular concept for the long-term coexistence of Th2 and Th1 cell lineage characteristics in single memory T cells.