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.

• 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