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Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal T cells via TGF-?

ABSTRACT: In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-?1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells. Total RNA were isolated from purified human CD1c+ (BDCA1+) and CD141+ (BDCA3+) mDCs sorted from different tissues, including human blood, spleen and lungs of humanized mice, and human lungs. Eighteen samples in total were analyzed from different donors and tissues.

ORGANISM(S): Homo sapiens

SUBMITTER: Chun Yu

PROVIDER: E-GEOD-43184 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal T cells via TGF-β

Project description:In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-β1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells.

2013-04-04 | GSE43184 | GEO

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Project description:Human immune cell subsets develop in immunodeficient mice following reconstitution with human CD34+ haematopoietic stem cells. These “humanized” mice are useful models to study human immunology and human-tropic infections, autoimmunity and cancer. However, some human immune cell subsets are unable to fully develop or acquire full functional capacity due to a lack of cross-reactivity of many growth factors and cytokines between species. “Classical” (c) DC arise from a separate precursor to monocytes and initiate and direct T cell responses. In mice they can be further categorized into cDC1, which mediate Th1 and CD8+ T cell responses, and cDC2, which mediate Th2 and Th17 responses. The gene expression profiles and phenotype human CD141+ DC and CD1c+ DC subsets align with mouse cDC1 and cDC2 respectively but there are also key interspecies differences. Human CD141+ DC and CD1c+ DC develop in humanized mice but the extent to which they resemble their human blood counterparts is not yet known. We therefore analyzed the gene expression profiles of CD141+ DC and CD1c+ DC in humanized mice and demonstrated that they closely resemble those in human blood, making this an attractive model in which to study human DC in vitro or on vivo. We further used this model to explore changes in DC subsets after activation with TLR3 and TLR7/8 ligands, poly I:C and R848 in vivo. A core panel of genes consistent with DC maturation status were upregulated by both subsets. R848 specifically upregulated genes associated with Th17 responses by CD1c+ DC, whilst poly I:C upregulated IFN-λ genes specifically by CD141+ DC. Thus CD141+ DC and CD1c+ DC share a similar activation profiles in vivo but also have induce unique signatures that support specialized roles in CD8+ T cell priming and Th17 responses respectively. '

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Gene array analysis of human adult lung antigen presenting cells.

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