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

Front Immunol. 2018 May 23:9:1127. doi: 10.3389/fimmu.2018.01127. eCollection 2018.

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.

Keywords: B cells; acute viral infection; follicular helper T cells; germinal center; mechanistic target of rapamycin complex 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • CD3 Complex / metabolism
  • Cell Differentiation / immunology*
  • Cell Lineage
  • Cell Movement / immunology*
  • Computational Biology / methods
  • Disease Models, Animal
  • Gene Expression Profiling
  • Humans
  • Immunity, Humoral
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Mechanistic Target of Rapamycin Complex 2 / metabolism*
  • Mice
  • Mice, Transgenic
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Virus Diseases / immunology*
  • Virus Diseases / metabolism*
  • Virus Diseases / virology

Substances

  • Biomarkers
  • CD3 Complex
  • Inducible T-Cell Co-Stimulator Protein
  • Mechanistic Target of Rapamycin Complex 2