Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes

Abstract

SummaryEpidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) ‐stimulated CD4 T lymphocytes have been investigated previously, but 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 naive 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 granulocyte–macrophage colony‐stimulating factor (GM‐CSF). The capacity of these mDCs to stimulate naive 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 interferon‐γ (IFN‐γ)‐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 IFN‐γ + cells. The secretion of tumour necrosis factor‐α, interleukin‐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 naive 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.

SARS‐CoV‐2 infection, COVID‐19 pathogenesis, and exposure to air pollution: What is the connection?

“…223 Myeloid dendritic cells exposed to urban PM enhanced naive CD8 + T cell priming, resulting in increased secretion of granyzme A and B. 224 Increased production of proinflammatory cytokines by CD8 + T cells responding to a viral infection could result in damage to bystander cells and inflammation amplification.…”

CD8+Tc2 cells: underappreciated contributors to severe asthma

“…Likewise, IL-33 potently enhances antiviral CD8 + T-cell responses [87]. An association of CD8 + cells with cigarette use [56] suggests that smoke may also activate CD8 + cells, while Tc2 cells in both mice and humans express perforin and granzyme [88] and induction of granzyme A mRNA and protein have been demonstrated in response to diesel fume particulates in human bronchoscopy samples [89].…”

Airway dendritic cell maturation in children exposed to air pollution

“…The capacity of pollutants to stimulate DC maturation is not limited to PM since Alexis et al reported increased expression of CD80 in response to either LPS or ozone [16,17]. Most recently Pfeffer et al reported increased expression of CD83 (an alternative maturation marker) and subsequent enhanced priming of CD8 T lymphocytes by ultrafine PM exposed human DCs [18].…”