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Dendritic Cell-Mediated T Cell Proliferation -A Functional Bioindicator of Inflammatory Source-Specific Particulate Matter
Citation:
WILLIAMS, M. A., M. J. DANIELS, AND T. J. Smith. Dendritic Cell-Mediated T Cell Proliferation -A Functional Bioindicator of Inflammatory Source-Specific Particulate Matter. Presented at Socciety of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
The immunotoxicological and allergic sensitization effects of ambient particulate matter (PM) and diesel exhaust particles is suspected from well controlled animal model studies and human research studies. Airborne pollutants are thought to behave as immunological adjuvants that may exacerbate pre-existing disease or provoke induction of disease like asthma following exposure lung to infectious agents like respiratory viruses. A specialized immunological cell termed the dendritic cell, is thought to mediate many of the immunological and inflammatory pathways of airways disease. Dendritic cells are very sensitive to changes in their local environment. We report on the utility of dendritic cells as a predictive and high throughput screening tool in hazard identification and risk assessment of novel PM species
Description:
Previously we found that dendritic cells (DC) were sensitive functional bioindicators of ambient PM (APM) exposure mediating Th2-allergic inflammation in the draining lymph nodes. Here, the ability of bone-marrow-derived DC (DC) and putative BM-derived basophils (Ba) to present antigen and activate autologous T cells following exposure to source-specific PM was assessed. DC and Ba propagated from female OVA-specific C57B1/6J OT-II.2 mice whose T cell receptors were transgenic for the chicken ovalbumin peptide OVA323-339. OVA-specific CD62L+ CD4+ T cells were purified from lymph nodes by immunomagnetic selection. DC or Ba were stimulated with APM, environmental diesel PM (DEP) or emission-source diesel PM (EPAx) for 24h, washed then loaded with/without endotoxin-free OVA (50ug/ml,4h) prior to co-culture for 5d with T cells and assessed for T cell activation by both bromodeoxyuridine uptake and Th1/Th2 cytokine responses. PM and DEP exposure resulted in functional maturation of DC and BA and provoked a Th2-skewed response. DC but not Ba promoted enhanced T cell activation with exposure to APM or LPS alone compared to "resting" DC. Moreover, exposure of DC to APM or DEP followed by OVA, enhanced T cell activation compared to control DC or DC stimulated with LPS or CD40L (positive controls). While Ba could stimulate T cells, DC responses were more sensitive to PM exposure. We conclude that DC are activated on exposure to APM and stimulate enhanced CD4+ T cell activation in the absence of OVA antigen loading. In DC primed with APM or DEP and subsequently loaded with OVA, T cell activation was markedly enhanced as compared non-OVA pulsed DC or DC not exposed to PM. The autologous OTII.2 DC/T cell antigen presentation assay is a sensitive bioindicator of the immunotoxic effects of environmental pollutant particles in vitro. This assay could be applied to hazard identification and risk assessment of previously untested PM species. (This abstract does not reflect EPA policy).