Impaired Proliferation of CD8+ T Cells Stimulated with Monocyte-Derived Dendritic Cells Previously Matured with Thapsigargin-Stimulated LAD2 Human Mast Cells
Language English Country Egypt Media electronic-ecollection
Document type Journal Article
PubMed
39056014
PubMed Central
PMC11272405
DOI
10.1155/2024/5537948
Knihovny.cz E-resources
- MeSH
- Lymphocyte Activation * drug effects immunology MeSH
- Cell Differentiation * drug effects MeSH
- Cell Line MeSH
- Hepatitis A Virus Cellular Receptor 2 metabolism MeSH
- CD8-Positive T-Lymphocytes * immunology drug effects MeSH
- Cytokines metabolism MeSH
- Dendritic Cells * immunology drug effects metabolism MeSH
- Imidazoles pharmacology MeSH
- Humans MeSH
- Mast Cells * immunology drug effects metabolism MeSH
- Monocytes immunology drug effects metabolism MeSH
- Cell Proliferation * drug effects MeSH
- Thapsigargin * pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Hepatitis A Virus Cellular Receptor 2 MeSH
- Cytokines MeSH
- HAVCR2 protein, human MeSH Browser
- Imidazoles MeSH
- Thapsigargin * MeSH
CD8+ T cells are essential for adaptive immunity against infection and tumors. Their ability to proliferate after stimulation is crucial to their functionality. Dendritic cells (DCs) are professional antigen-presenting cells that induce their proliferation. Here, we show that thapsigargin-induced LAD2 mast cell (MC) line-released products can impair the ability of monocyte-derived DCs to induce CD8+ T-cell proliferation and the generation of Th1 cytokine-producing T cells. We found that culture medium conditioned with LAD2 MCs previously stimulated with thapsigargin (thapsLAD2) induces maturation of DCs as determined by the maturation markers CD80, CD83, CD86, and HLA-DR. However, thapsLAD2-matured DCs produced no detectable TNFα or IL-12 during the maturation. In addition, although their surface expression of PD-L1 was comparable with the immature or TLR7/8-agonist (R848)-matured DCs, their TIM-3 expression was significantly higher than in immature DCs and even much higher than in R848-matured DCs. In addition, contrary to R848-matured DCs, the thapsLAD2-matured DCs only tended to induce enhanced proliferation of CD4+ T cells than immature DCs. For CD8+ T cells, this tendency was not even detected because thapsLAD2-matured and immature DCs comparably induced their proliferation, which contrasted with the significantly enhanced proliferation induced by R848-matured DCs. Furthermore, these differences were comparably recapitulated in the ability of the tested DCs to induce IFNγ- and IFNγ/TNFα-producing T cells. These findings show a novel mechanism of MC-mediated regulation of adaptive immune responses.
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