Portal de Periódicos da CAPES

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

2016; Cell Press; Volume: 44; Issue: 2 Linguagem: Inglês

10.1016/j.immuni.2015.11.017

1097-4180

André Ballesteros‐Tato, Troy D. Randall, Frances E. Lund, Rosanne Spolski, Warren J. Leonard, Beatriz León,

Allergic Rhinitis and Sensitization

Highlights•HDM sensitization does not prime Th2 cells, but induces IL-4-committed Tfh cells•Ag-presenting B cells synergize with DCs to prime Tfh cells during HDM sensitization•IL-4-committed Tfh cells are precursors of effector Th2 cells after HDM rechallenge•Depletion of IL-4-committed Tfh cells prevents Th2 cell-mediated immunity to HDMSummaryExposure 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.Graphical abstract