Migration and Maturation of Human Colonic Dendritic Cells

Bell, Sally; Rigby, Rachael; English, Nicholas R.; Mann, Steven D.; Knight, Stella C.; Kamm, Michael A.; Stagg, Andrew J.

doi:10.4049/jimmunol.166.8.4958

Cited by 151 publications

(145 citation statements)

References 43 publications

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“…However, in line with our results, experiments with human intestinal mucosal explants have shown that TNF, IL-8, and IL-10 are produced in response to E. coli but not in response to Lactobacillus casei (11). Furthermore, the gut mucosal DCs predominantly consist of myeloid DCs, which presumably are of monocyte origin (7). The differences in the cytokine responses of monocytes and DCs could not be explained by differences in phagocytic capacities, as the bacteria were equally well phagocytosed by monocytes and DCs.…”

Section: Discussionsupporting

confidence: 77%

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Karlsson¹,

Larsson²,

Wold

et al. 2004

Infect Immun

118

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The normal gastrointestinal bacterial flora is crucial for the maturation of acquired immunity via effects on antigen-presenting cells (APCs). Here we investigated how two types of APCs, monocytes and dendritic cells (DCs), react to different bacterial strains typical of the commensal intestinal microflora. Purified human monocytes and monocyte-derived DCs were stimulated with UV-inactivated gram-positive (Lactobacillus plantarum and Bifidobacterium adolescentis) and gram-negative (Escherichia coli and Veillonella parvula) bacterial strains. Monocytes produced higher levels of interleukin 12p70 (IL-12p70) and tumor necrosis factor (TNF), as detected by an enzyme-linked immunosorbent assay, in response to L. plantarum than in response to E. coli and V. parvula. In contrast, DCs secreted large amounts of IL-12p70, TNF, IL-6, and IL-10 in response to E. coli and V. parvula but were practically unresponsive to L. plantarum and B. adolescentis. The lack of a response to the gram-positive strains correlated with lower surface expression of Toll-like receptor 2 (TLR2) on DCs than on monocytes. The surface expression of TLR4 on DCs was undetectable when it was analyzed by flow cytometry, but blocking this receptor decreased the TNF production in response to V. parvula, indicating that TLR4 is expressed at a low density on DCs. Gamma interferon increased the expression of TLR4 on DCs and also potentiated the cytokine response to the gram-negative strains. Our results indicate that when monocytes differentiate into DCs, their ability to respond to different commensal bacteria dramatically changes, and they become unresponsive to probiotic gram-positive bacteria. These results may have important implications for the abilities of different groups of commensal bacteria to regulate mucosal and systemic immunity.

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Section: Discussionsupporting

confidence: 77%

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Karlsson¹,

Larsson²,

Wold

et al. 2004

Infect Immun

118

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“…Colonic Vd2T cells were relatively frequent and widely interspersed throughout the lamina propria. Accordingly, Vd2T cells could also be identified by flow cytometry in LPMC that migrated out of colonic and small intestinal biopsy tissue (32). Total lamina propria lymphocytes contained a distinct subset of Vd2T cells (Fig.…”

Section: Phosphoantigen-responsive Vd2t Cells Populate the Human Intementioning

confidence: 98%

“…The procedure for obtaining lamina propria mononuclear cells (LPMC) from human intestinal biopsies has been described in detail elsewhere (32). Briefly, biopsies of colonic tissue were collected into cold, Dutch-Modified RPMI 1640 medium (Sigma-Aldrich).…”

Section: Lamina Propria Mononuclear Cellsmentioning

confidence: 99%

Proinflammatory Vδ2+ T Cells Populate the Human Intestinal Mucosa and Enhance IFN-γ Production by Colonic αβ T Cells

McCarthy

Bashir

Vossenkämper

et al. 2013

The Journal of Immunology

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In nonhuman primates, Vγ9Vδ2+ (Vδ2)T cells proliferate and accumulate in mucosal tissues following microbial activation. Human Vδ2T cells produce proinflammatory cytokines in response to bacterial species that colonize the gut, but the role played by Vδ2T cells in intestinal immunity is unknown. We hypothesized that circulating Vδ2T cells can populate the human intestine and contribute to mucosal inflammation. Cell suspensions prepared from peripheral blood and intestinal biopsies were stimulated with microbial phosphoantigen (1-hydroxy-2-methyl-2-buten-4-yl 4-diphosphate [HDMAPP]) and analyzed by flow cytometry to determine Vδ2T cell phenotype, cytokine production, and proliferative potential. Circulating Vδ2T cells expressed gut-homing integrin α4β7 (>70%), which was coexpressed with skin-associated cutaneous leukocyte Ag by up to 15% of the total population. However, Vδ2T cell activation with HDMAPP and exposure to retinoic acid (signaling via retinoic acid receptor α) increased α4β7 expression and enhanced binding to mucosal addressin cell adhesion molecule-1 in vitro while simultaneously suppressing cutaneous leukocyte Ag, thereby generating a committed gut-tropic phenotype. Confocal microscopy and flow cytometry identified frequent Vδ2T cells that migrated out of human intestinal biopsies and comprised both CD103+ and CD103− subsets that produced TNF-α and IFN-γ upon phosphoantigen exposure, with more frequent cytokine-producing cells in the CD103− population. Activated intestinal Vδ2T cells expressed CD70 and HLA-DR but were unable to drive the proliferation of allogeneic naive CD4+ T cells. Instead, phosphoantigen-activated CD103− Vδ2T cells increased T-bet expression and enhanced IFN-γ production by autologous colonic αβ T cells via an IFN-γ–dependent mechanism. These data demonstrate that circulating Vδ2T cells display enhanced gut-homing potential upon microbial activation and populate the human intestinal mucosa, generating functionally distinct CD103+ and CD103− subsets that can promote inflammation by colonic αβ T cells.

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“…Immature or mature DCs (1 Â 10 5 ) were incubated at 371C in a complete medium containing 1 mg ml À1 FITC-dextran. A control experiment was performed by incubating the cells at 41C for 1 h. After incubation, the cells were washed twice with ice-cold PBS and then subjected to flow cytometry analysis (Bell et al, 2001). …”

Section: Endocytosis Assaymentioning

confidence: 99%

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

et al. 2004

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Transduction of recombinant adenovirus into dendritic cells (DCs) is a promising new tool for cancer vaccine development. Here, we report that an adenovirus vector carrying hepatocellular carcinoma (HCC) antigen HCA661 and infected into DCs generates T-cell immunity against hepatoma cells. HCA661 is a novel cancer/testis (CT) antigen screened by SEREX from sera of an HCC patient. We constructed a recombinant adenovirus expressing the full-length cDNA of HCA661 gene and then transduced immature DCs, which had been generated with GM-CSF and IL-4 from peripheral blood mononuclear cell of HLA-A2 þ healthy donors. The resulting adenovirus-transduced DCs differentiated in the presence of monocyte-conditioned medium and poly [I] : poly [C], expressing the surface markers of mature DCs, including CD83, CD80, CD86 and HLA-DR. After maturation, the transduced DCs transcribed HCA661 mRNA and were able to prime the naïve T cells to become cytotoxic T lymphocytes (CTLs). Intracellular flow cytometry and enzyme-linked immunospot assay showed that these CTLs were able to target a hepatoma cell line, HepG2, which is HLA-A2 and HCA661 positive. In summary, we found that this recombinant adenovirus can help to induce DC maturation and these mature DCs can activate T cells to target hepatoma cells. Therefore, this recombinant adenovirus may have potential for use in liver cancer immunotherapy.

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Migration and Maturation of Human Colonic Dendritic Cells

Cited by 151 publications

References 43 publications

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Proinflammatory Vδ2+ T Cells Populate the Human Intestinal Mucosa and Enhance IFN-γ Production by Colonic αβ T Cells

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

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