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Immunity. 2016 Feb 16;44(2):259-73. doi: 10.1016/j.immuni.2015.11.017. Epub 2016 Jan 26.

T Follicular Helper Cell Plasticity Shapes Pathogenic T Helper 2 Cell-Mediated Immunity to Inhaled House Dust Mite.

Author information

1
Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
2
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
3
Laboratory of Molecular Immunology, National Heart, Lung and Blood institute, Bethesda, MD 20892, USA.
4
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: bleon@uab.edu.

Abstract

Exposure to environmental antigens, such as house dust mite (HDM), often leads to T helper 2 (Th2) cell-driven allergic responses. However, the mechanisms underlying the development of these responses are incompletely understood. We found that the initial exposure to HDM did not lead to Th2 cell development but instead promoted the formation of interleukin-4 (IL-4)-committed T follicular helper (Tfh) cells. Following challenge exposure to HDM, Tfh cells differentiated into IL-4 and IL-13 double-producing Th2 cells that accumulated in the lung and recruited eosinophils. B cells were required to expand IL-4-committed Tfh cells during the sensitization phase, but did not directly contribute to disease. Impairment of Tfh cell responses during the sensitization phase or Tfh cell depletion prevented Th2 cell-mediated responses following challenge. Thus, our data demonstrate that Tfh cells are precursors of HDM-specific Th2 cells and reveal an unexpected role of B cells and Tfh cells in the pathogenesis of allergic asthma.

PMID:
26825674
PMCID:
PMC4758890
DOI:
10.1016/j.immuni.2015.11.017
[Indexed for MEDLINE]
Free PMC Article

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