Mucosal CD8 Memory T Cells are selected in the periphery by an MHC Class I Molecule

The presence of immune memory at pathogen entry sites is a prerequisite for protection. Nevertheless, the mechanisms that warrant immunity at peripheral interfaces are not understood. Here we show that the non-classical MHC class I molecule, the thymus leukemia antigen (TL), induced on dendritic cells together with CD8aa on activated CD8αβ+T cells, mediates affinity-based selection of memory precursor cells. Furthermore, constitutive expression of TL on epithelial cells continues the selection of mature CD8αβ memory T cells. The TL-CD8αα-driven memory process is essential for the generation of memory CD8αß T cells in the intestine and leads to the accumulation of highly antigen sensitive CD8αβ memory T cells that form the first line of defense at the largest entry port for pathogens

Unique lamina propria stromal cells imprint the functional phenotype of mucosal dendritic cells

Mucosal dendritic cells (DCs) in the intestine acquire the unique capacity to produce retinoic acid (RA), a vitamin A metabolite that induces gut tropism and regulates the functional differentiation of the T cells they prime. Here we identified a stromal cell (SC) population in the intestinal lamina propria (LP), which is capable of inducing RA production in DCs in a RA- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent fashion. Unlike DCs, LP SCs constitutively expressed the enzymatic machinery to produce RA even in the absence of dietary vitamin A but were not able to do so in germ-free mice implying regulation by microbiota. Interestingly, DCs promoted GM-CSF production by the SCs indicating a two-way crosstalk between both cell types. Furthermore, RA-producing LP SCs and intestinal DCs localized closely in vivo suggesting that the interactions between both cell types might play an important role on the functional education of migratory DCs and therefore in the regulation of immune responses towards oral and commensal antigens

The chemotherapeutic drug oxaliplatin differentially affects blood DC function dependent on environmental cues.

Item does not contain fulltextIt has become evident that the tumor microenvironment plays a pivotal role in the maintenance of cancerous growth. One of the acquired functions of the tumor microenvironment is the suppression of immune responses. Indeed, blocking the inhibitory pathways operational in the microenvironment results in enhanced T-cell-dependent, anti-tumor immunity. Chemotherapeutic drugs not only directly kill tumor cells but also shape the tumor microenvironment and potentiate anti-tumor immunity. Here, we demonstrate that the chemotherapeutic compound oxaliplatin acts as a double-edged sword. Besides killing tumor cells, oxaliplatin bolsters immunosuppressive pathways, resulting in decreased activation of T cells by human plasmacytoid dendritic cells (pDCs). Exposure to oxaliplatin markedly increased expression of the T-cell inhibitory molecule programmed death receptor-ligand 1 (PD-L1) on human pDCs and also TLR9-induced IFNalpha secretion. Furthermore, oxaliplatin decreased TLR-induced STAT1 and STAT3 expression, and NF-kappaB-mediated responses. The oxaliplatin induced upregulation of PD-L1 and downregulation of costimulatory molecules CD80 and CD86 resulted in decreased T-cell proliferation. Our results demonstrate that platinum-based anticancer drugs adapt TLR-induced signaling in human pDCs and myeloid DCs (mDCs), thereby downgrading their immunostimulatory potential.1 juli 201