title: Diesel exhaust, carbon black, and silica particles display distinct Th1/Th2 modulating activity.
abstract: Certain particulate air pollutants may play an important role in the increasing prevalence of respiratory allergy by stimulating T helper 2 cell (Th2)-mediated immune responses to common antigens. The study described here examined different particles, diesel exhaust particles (DEP), carbon black particles (CBP), and silica particles (SIP) for their immunomodulating capacity in both primary and secondary immune responses in female BALB/C mice. The primary response was studied after subcutaneous injection of 1 mg of particle together with 10 microgram of reporter antigen TNP-OVA (2,4,6-trinitrophenyl coupled to ovalbumin) into the hind paw. Interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) production was assessed in the popliteal lymph node (PLN) at Day 2 and Day 5 after injection by flow cytometry and ELISA. The number of IL-4-containing CD4(+) T cells increased between Day 2 and Day 5 in DEP- and CBP-exposed mice, in contrast to SIP-treated animals. IL-4 production by cultured PLN cells was also significantly increased for DEP- and CBP-treated animals. The secondary response was studied in different organs after an intranasal challenge with TNP-OVA (50 microgram), which was given 4 weeks after the initial subcutaneous injection. Five days after challenge the number of antibody-forming cells (AFCs) was assessed in peribronchial lymph nodes (PBLN), spleen, bone marrow, and PLN, and antibody levels were determined in weekly obtained blood samples. It appeared that all particles acted as adjuvant, but the different particles stimulated distinct types of immune responses to TNP-OVA. DEP-treated animals show high IgG1 and IgE levels in serum and high IgG1 and IgE-forming AFC numbers in PBLN, bone marrow, and spleen. CBP-treated animals show even higher IgG1 and IgE levels and AFC numbers, and in addition display IgG2a production. SIP-injected animals display predominantly IgG2a responses. It is concluded that DEP are able to skew the immune response toward the T helper 2 (Th2) side, whereas SIP stimulate a Th1 response and CBP have a mixed activity, stimulating both Th1 and Th2 responses in this model.
authors.affiliation: RITOX Immunotoxicology, Utrecht University, Utrecht, 3508 TD, The Netherlands. m.vanzijverden@ritox.vet.uu.nl
authors.forename: M
authors.initials: M
authors.lastname: van Zijverden
authors.forename: A
authors.initials: A
authors.lastname: van der Pijl
authors.forename: M
authors.initials: M
authors.lastname: Bol
authors.forename: F A
authors.initials: FA
authors.lastname: van Pinxteren
authors.forename: C
authors.initials: C
authors.lastname: de Haar
authors.forename: A H
authors.initials: AH
authors.lastname: Penninks
authors.forename: H
authors.initials: H
authors.lastname: van Loveren
authors.forename: R
authors.initials: R
authors.lastname: Pieters
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000393:Air Pollutants / Q000276:immunology / Q000633:toxicity*; D000818:Animals; D000918:Antibody Specificity; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen; D001985:Bronchial Provocation Tests; D019013:CD40 Antigens / Q000096:biosynthesis / Q000276:immunology; D002244:Carbon / Q000276:immunology / Q000633:toxicity*; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D012822:Silicon Dioxide / Q000276:immunology / Q000633:toxicity*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000276:Adjuvants, Immunologic; D000393:Air Pollutants; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D001335:Vehicle Emissions; C038600:trinitrophenyl-ovalbumin; D015847:Interleukin-4; D007073:Immunoglobulin E; D002244:Carbon; D012822:Silicon Dioxide; D007371:Interferon-gamma; D010047:Ovalbumin