Diesel exhaust, carbon black, and silica particles display distinct Th1/Th2 modulating activity

Certain particulate air pollutants may play an important role in the increa sing prevalence of respiratory allergy by stimulating T helper 2 cell (Th2) -mediated immune responses to common antigens. The study described here exa mined different particles, diesel exhaust particles (DEP), carbon black par ticles (CBP), and silica particles (SIP) for their immunomodulating capacit y in both primary and secondary immune responses in female BALB/C mice. The primary response was studied after subcutaneous injection of 1 mg of parti cle together with 10 mug of reporter antigen TNP-OVA (2,4,6-trinitrophenyl coupled to ovalbumin) into the hind paw. Interferon-gamma (IFN-gamma) and i nterleukin 4 (IL-4) production was assessed in the popliteal lymph node (PL N) at Day 2 and Day 5 after injection by flow cytometry and ELISA. The numb er of IL-4-containing CD4(+) T cells increased between Day 2 and Day 5 in D EP- and CBP-exposed mice, in contrast to SIP-treated animals. IL-4 producti on by cultured PLN cells was also significantly increased for DEP- and CBP- treated animals. The secondary response was studied in different organs aft er an intranasal challenge with TNP-OVA (50 mug), which was given 4 weeks a fter the initial subcutaneous injection. Five days after challenge the numb er of antibody-forming cells (AFCs) was assessed in peribronchial lymph nod es (PBLN), spleen, bone marrow, and PLN, and antibody levels were determine d 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 s pleen. CBP-treated animals show even higher IgG1 and IgE levels and AFC num bers, and in addition display IgG2a production. SIP-injected animals displa y 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, (C) 2000 Academic Press.