title: Differential control of CD4(+) T-cell subsets by the PD-1/PD-L1 axis in a mouse model of allergic asthma.
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.
authors: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: Jaclyn W
authors: JW
authors: McAlees
authors: Stephane
authors: S
authors: Lajoie
authors: Krista
authors: K
authors: Dienger
authors: Alyssa A
authors: AA
authors: Sproles
authors: Phoebe K
authors: PK
authors: Richgels
authors: Yanfen
authors: Y
authors: Yang
authors: Marat
authors: M
authors: Khodoun
authors: Miyuki
authors: M
authors: Azuma
authors: Hideo
authors: H
authors: Yagita
authors: Patricia C
authors: PC
authors: Fulkerson
authors: Marsha
authors: M
authors: Wills-Karp
authors: Ian P
authors: IP
authors: Lewkowich
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018664:Interleukin-12 / Q000097:blood; D008168:Lung / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000037:antagonists & inhibitors; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D016207:Cytokines; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D018664:Interleukin-12
keywords: Airway hyperreactivity; Asthma; Cytokines; PD-1/PD-L1; Th1 response; Th17 response; Th2 response
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