Exposure to allergen and diesel exhaust particles potentiates secondary allergen-specific memory responses, promoting asthma susceptibility.
BACKGROUND
Exposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEPs), increases the risk of asthma and asthma exacerbation; however, the underlying mechanisms remain poorly understood.


OBJECTIVE
We sought to examine the effect of DEP exposure on the generation and persistence of allergen-specific memory T cells in asthmatic patients and translate these findings by determining the effect of early DEP exposure on the prevalence of allergic asthma in children.


METHODS
The effect of DEPs on house dust mite (HDM)-specific memory responses was determined by using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort were analyzed to determine the effect of DEP exposure on asthma outcomes.


RESULTS
DEP coexposure with HDM resulted in persistent TH2/TH17 CD127(+) effector/memory cells in the lungs, spleen, and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased TH2 cytokine levels in mice that had been previously exposed to both HDM and DEPs versus those exposed to HDM alone. On the basis of these data, we examined whether DEP exposure was similarly associated with increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort. Early-life exposure to high DEP levels was associated with significantly increased asthma prevalence among allergic children but not among nonallergic children.


CONCLUSIONS
These findings suggest that DEP exposure results in accumulation of allergen-specific TH2/TH17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma.
Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, Ohio.
Eric B
EB
Brandt
Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, Ohio.
Jocelyn M
JM
Biagini Myers
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, Ohio.
Thomas H
TH
Acciani
Division of Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, Ohio.
Patrick H
PH
Ryan
Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, Ohio.
Umasundari
U
Sivaprasad
Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, Ohio.
Brandy
B
Ruff
Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, Ohio; Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio.
Grace K
GK
LeMasters
Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio.
David I
DI
Bernstein
Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio.
James E
JE
Lockey
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, Ohio.
Timothy D
TD
LeCras
Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, Ohio. Electronic address: Gurjit.Hershey@cchmc.org.
Gurjit K
GK
Khurana Hershey
D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007156:Immunologic Memory; D007223:Infant; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D018448:Models, Immunological; D052638:Particulate Matter / Q000009:adverse effects*; D039981:Pyroglyphidae / Q000737:chemistry / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D001335:Vehicle Emissions
D000485:Allergens; D052638:Particulate Matter; D001335:Vehicle Emissions; D007073:Immunoglobulin E
Allergic asthma; children; diesel exhaust particle; house dust mite; memory; recall; traffic pollution