Activation of Natural T Lymphocytes by Diesel Exhaust Particulates Leads to Their Production of Interleukin-4 and TH2 Lymphocyte Differentiation to Allergen

EPA Grant Number: R825702C010
Subproject: this is subproject number 010 , established and managed by the Center Director under grant R825702
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Environmental Lung Disease Center (National Jewish Medical and Research Center)
Center Director: Mason, Robert J.
Title: Activation of Natural T Lymphocytes by Diesel Exhaust Particulates Leads to Their Production of Interleukin-4 and TH2 Lymphocyte Differentiation to Allergen
Investigators: Routes, John M. , Borish, Larry
Institution: National Jewish Medical and Research Center
EPA Project Officer: Chung, Serena
Project Period: February 16, 1998 through February 28, 2003 (Extended to February 28, 2004)
RFA: Environmental Lung Disease Center (National Jewish Medical and Research Center) (1998) RFA Text |  Recipients Lists
Research Category: Targeted Research

Objective:

The prevalence of atopic diseases is increasing in industrialized societies worldwide, a process linked to exposure to environmental, airborne pollution. Recent murine and human studies demonstrate that diesel exhaust particles (DEP) may be the component of air pollution most responsible for this increase in atopic diseases. Human studies show that DEP increases allergen specific IgE in both atopic and non-atopic subjects. The long- range goals of our labs are to define the molecular and immune basis for the capacity of diesel exhaust particles (DEP) to enhance allergen-specific IgE responses. We hypothesize that the capacity of DEP to enhance allergen- specific IgE response is mediated through its capacity to augment early IL-4 production by natural T cells (NT cells). Studies in this proposal will specifically test this hypothesis and also determine that DEP can induce allergen-specific IgE production in both allergy-prone and allergy-resistant strains of mice. The final goal of this proposal is to develop a biologically-relevant, inhalation challenge protocol in mice using DEP.

Specific Aim 1: Determine if natural T cells are responsible for the enhanced allergen-specific production of IgE-mediated by DEP.

Supplemental Keywords:

RFA, Health, Scientific Discipline, Air, particulate matter, Toxicology, Environmental Chemistry, Health Risk Assessment, Risk Assessments, mobile sources, Allergens/Asthma, Disease & Cumulative Effects, Biochemistry, Atmospheric Sciences, ambient aerosol, ambient air quality, cars, particulates, motor vehicles, human health effects, vehicle emissions, motor vehicle emissions, T cells, ambient air, exposure, air pollution, automobiles, automotive exhaust, diesel exhaust, emissions, interluken, Lymphocytes, environmental health effects, interleukin, airborne pollutants, automotive, chronic health effects, human exposure, inhalation, diesel, harmful environmental agents, inhaled, vehicular exhaust, ambient particulates, diesel exhaust particles, fuels, allergens, allergic response, atmospheric chemistry, human health risk

Progress and Final Reports:

  • 1998
  • 1999
  • 2000
  • 2001
  • 2002
  • 2003
  • Final

  • Main Center Abstract and Reports:

    R825702    Environmental Lung Disease Center (National Jewish Medical and Research Center)

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R825702C001 SP-A and SP-D in Environmental Lung Disease
    R825702C003 Adaptation to Nitrogen Dioxide: Role of Altered Glycolytic Pathway Enzyme Expression and NF-κB-Dependent Cellular Defenses Against Apoptosis
    R825702C005 Inhalation of Particulate Matter Alters the Allergic Airway Response to Inhaled Allergen
    R825702C006 Particle-Induced Lung Inflammation and Extracellular EC-SOD
    R825702C007 Indoor-Outdoor Relationships of Airborne Particle Count and Endotoxin Concentrations
    R825702C008 The Role of Mitochondrial DNA Mutations in Oxidant-Mediated Lung Injury
    R825702C009 Immunopathogenesis of Hypersensitivity Pneumonitis in the Mouse
    R825702C010 Activation of Natural T Lymphocytes by Diesel Exhaust Particulates Leads to Their Production of Interleukin-4 and TH2 Lymphocyte Differentiation to Allergen
    R825702C011 Latex Antigen Levels During Powdered and Powderless Glove Use
    R825702C012 Adjuvant Effects of Ozone in a Model of Allergen-Induced Airway Inflammation and Hyperresponsiveness
    R825702C013 Acute Exposure to Particulate Air Pollution in Childhood Asthma
    R825702C014 Mechanisms of Ozone Toxicity to the Lung