• Jaclyn W McAlees, Stephane Lajoie, Krista Dienger, Alyssa A Sproles, Phoebe K Richgels, Yanfen Yang, Marat Khodoun, Miyuki Azuma, Hideo Yagita, Patricia C Fulkerson, Marsha Wills-Karp, and Ian P Lewkowich.
• Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
• Eur. J. Immunol. 2015 Apr 1; 45 (4): 1019-29.

AbstractStudies 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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