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Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and COPD, which are both associated with viral respiratory infections. The effects of urban PM on dendritic cell (DC) stimulated CD4 T lymphocytes have been investigated previously, however little work has focused on CD8 T lymphocyte responses despite their importance in anti-viral immunity. To
address this, we examined the effects of UPM on DC-stimulated naïve CD8 T cell responses.

Expression of the maturation/activation markers CD83, CCR7, CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow-cytometry after stimulation with UPM in vitro in the presence/absence of GM-CSF. The capacity of these mDCs to stimulate naïve CD8 T lymphocyte responses in allogeneic co-culture was then assessed by measuring T cell cytokine secretion using cytometric bead array, and proliferation and frequency of IFNγ-producing T
lymphocytes by flow-cytometry.

Treatment of mDCs with UPM increased expression of CD83 and CCR7, but not MHC class I. In allogeneic co-cultures, UPM treatment of mDCs enhanced CD8 T cell proliferation and the frequency of IFNγ+ cells. The secretion of TNFα, IL-13, Granzyme A and Granzyme B were also increased. GM-CSF alone, and in concert with UPM, enhanced many of these T cell functions. The PM-induced increase in Granzyme A was confirmed in a human experimental diesel
exposure study.

These data demonstrate that UPM treatment of mDCs enhances priming of naïve CD8 T lymphocytes and increases production of pro-inflammatory cytokines. Such UPM-induced stimulation of CD8 cells may potentiate T-lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.
Original languageEnglish
Early online date28 Nov 2017
Publication statusE-pub ahead of print - 28 Nov 2017


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