Abstract
Studies examining the role of PD-1 family members in allergic asthma have yielded conflicting results. Using a mouse model of allergic asthma, we demonstrate that blockade of PD-1/PD-L1 has distinct influences on different CD4+ T-cell subsets. PD-1/PD-L1 blockade enhances airway hyperreactivity (AHR), not by altering the magnitude of the underlying Th2-type immune response, but by allowing the development of a concomitant Th17-type immune response. Supporting differential CD4+ T-cell responsiveness to PD-1-mediated inhibition, naïve PD-1-/- mice displayed elevated Th1 and Th17 levels, but diminished Th2 cytokine levels, and ligation of PD-1 in WT cells limited cytokine production by in vitro polarized Th1 and Th17 cells, but slightly enhanced cytokine production by in vitro polarized Th2 cells. Furthermore, PD-1 ligation enhanced Th2 cytokine production by naïve T cells cultured under nonpolarizing conditions. These data demonstrate that different CD4+ T-cell subsets respond differentially to PD-1 ligation and may explain some of the variable results observed in control of allergic asthma by the PD-1 family members. As the PD-1/PD-L1 axis limits asthma severity by constraining Th17 cell activity, this suggests that severe allergic asthma may be associated with a defective PD-1/PD-L1 regulatory axis in some individuals.
Original language | English (US) |
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Pages (from-to) | 1019-1029 |
Number of pages | 11 |
Journal | European Journal of Immunology |
Volume | 45 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1 2015 |
Keywords
- Airway hyperreactivity
- Asthma
- Cytokines
- PD-1/PD-L1
- Th1 response
- Th17 response
- Th2 response
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology