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Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD 8 T lymphocytes
Author(s) -
Pfeffer Paul E.,
Ho Tzer R.,
Mann Elizabeth H.,
Kelly Frank J.,
Sehlstedt Maria,
Pourazar Jamshid,
Dove Rosamund E.,
Sandstrom Thomas,
Mudway Ian S.,
Hawrylowicz Catherine M.
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12852
Subject(s) - t cell , immunology , granzyme b , biology , priming (agriculture) , cytokine , dendritic cell , cytotoxic t cell , immune system , in vitro , biochemistry , botany , germination
Summary Epidemiological 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 CD 4 T lymphocytes have been investigated previously, but little work has focused on CD 8 T‐lymphocyte responses despite their importance in anti‐viral immunity. To address this, we examined the effects of UPM on DC ‐stimulated naive CD 8 T‐cell responses. Expression of the maturation/activation markers CD 83, CCR 7, CD 40 and MHC class I on human myeloid DC s ( mDC s) 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 mDC s to stimulate naive CD 8 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 mDC s with UPM increased expression of CD 83 and CCR 7, but not MHC class I. In allogeneic co‐cultures, UPM treatment of mDC s enhanced CD 8 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 mDC s enhances priming of naive CD 8 T lymphocytes and increases production of pro‐inflammatory cytokines. Such UPM ‐induced stimulation of CD 8 cells may potentiate T‐lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.