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The Kinase Complex mTOR Complex 2 Promotes the Follicular Migration and Functional Maturation of Differentiated Follicular Helper CD4+ T Cells During Viral Infection.


ABSTRACT: Follicular helper CD4+ T (TFH) cells are critical for optimal B-cell-mediated humoral immunity by initiating, fueling, and sustaining germinal center reactions. The differentiation of TFH cells relies on multiple intrinsic and extrinsic factors; however, the details by which these factors are integrated to coordinate TFH differentiation are largely unknown. In this study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) viral infection, we demonstrate that mTOR complex 2 (mTORC2) kinase integrates TCR signaling and ICOS-mediated co-stimulation to promote late differentiation and functional maturation of virus-specific TFH cells. Specifically, mTORC2 functions to maintain TFH lineage specifications, including phenotypes, migratory characteristics, and functional properties. Thus, our results highlight the importance of mTORC2 in guarding TFH phenotypic and functional maturation.

SUBMITTER: Hao Y 

PROVIDER: S-EPMC5974104 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Kinase Complex mTOR Complex 2 Promotes the Follicular Migration and Functional Maturation of Differentiated Follicular Helper CD4<sup>+</sup> T Cells During Viral Infection.

Hao Yaxing Y   Wang Yifei Y   Liu Xiaobing X   Yang Xia X   Wang Pengcheng P   Tian Qin Q   Bai Qiang Q   Chen Xiangyu X   Li Zhirong Z   Wu Jialin J   Xie Zhunyi Z   Zhou Xinyuan X   Zhou Yuyang Y   Yin Zhinan Z   Wu Yuzhang Y   Ye Lilin L  

Frontiers in immunology 20180523


Follicular helper CD4<sup>+</sup> T (T<sub>FH</sub>) cells are critical for optimal B-cell-mediated humoral immunity by initiating, fueling, and sustaining germinal center reactions. The differentiation of T<sub>FH</sub> cells relies on multiple intrinsic and extrinsic factors; however, the details by which these factors are integrated to coordinate T<sub>FH</sub> differentiation are largely unknown. In this study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) viral infe  ...[more]

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