| 1. |
- Milling, S W F, et al.
(författare)
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Steady-state migrating intestinal dendritic cells induce potent inflammatory responses in naive CD4+ T cells.
- 2009
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Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 2:2, s. 156-65
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Tidskriftsartikel (refereegranskat)abstract
- Steady-state dendritic cells (DCs) migrating in the lymph from the intestine induce tolerance to harmless intestinal antigens, preventing inflammatory responses. To determine if such DCs are inherently tolerogenic we collected intestinal lymph DCs (L-DCs) by cannulation of the thoracic duct of rats after mesenteric lymphadenectomy, and examined their capacity to activate naive CD4+ lymphocytes in an allogeneic mixed leucocyte reaction. L-DCs stimulated strong proliferative responses, induced secretion of inflammatory cytokines including interferon-gamma, and induced FoxP3-positive lymphocytes to divide. To determine if the activated CD4+ T cells had been tolerized, they were rested and restimulated with irradiated splenocytes. The restimulated CD4+ T cells again proliferated and secreted inflammatory cytokines. These data demonstrate that the DCs, which migrate from the intestine in the steady state, are paradoxically able to induce strong inflammatory responses from naive T cells, despite their role in the maintenance of oral tolerance.
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| 2. |
- Cerovic, V, et al.
(författare)
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Intestinal CD103(-) dendritic cells migrate in lymph and prime effector T cells.
- 2013
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Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 6:1, s. 104-13
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal dendritic cells (DCs) continuously migrate through lymphatics to mesenteric lymph nodes where they initiate immunity or tolerance. Recent research has focused on populations of intestinal DCs expressing CD103. Here we demonstrate, for the first time, the presence of two distinct CD103(-) DC subsets in intestinal lymph. Similar to CD103(+) DCs, these intestine-derived CD103(-) DCs are responsive to Flt3 and they efficiently prime and confer a gut-homing phenotype to naive T cells. However, uniquely among intestinal DCs, CD103(-) CD11b(+) CX(3)CR1(int) lymph DCs induce the differentiation of both interferon-γ and interleukin-17-producing effector T cells, even in the absence of overt stimulation. Priming by CD103(-) CD11b(+) DCs represents a novel mechanism for the rapid generation of effector T-cell responses in the gut. Therefore, these cells may prove to be valuable targets for the treatment of intestinal inflammation or in the development of effective oral vaccines.
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| 3. |
- Cerovic, V, et al.
(författare)
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Lymph-borne CD8α(+) dendritic cells are uniquely able to cross-prime CD8(+) T cells with antigen acquired from intestinal epithelial cells.
- 2015
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Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 8, s. 38-48
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Tidskriftsartikel (refereegranskat)abstract
- Cross-presentation of cellular antigens is crucial for priming CD8(+) T cells, and generating immunity to intracellular pathogens-particularly viruses. It is unclear which intestinal phagocytes perform this function in vivo. To address this, we examined dendritic cells (DCs) from the intestinal lymph of IFABP-tOVA 232-4 mice, which express ovalbumin in small intestinal epithelial cells (IECs). Among lymph DCs (LDCs) only CD103(+) CD11b(-) CD8α(+) DCs cross-present IEC-derived ovalbumin to CD8(+) OT-I T cells. Similarly, in the mesenteric lymph nodes (MLNs), cross-presentation of IEC-ovalbumin was limited to the CD11c(+) MHCII(hi) CD8α(+) migratory DCs, but absent from all other subsets, including the resident CD8α(hi) DCs. Crucially, delivery of purified CD8α(+) LDCs, but not other LDC subsets, into the MLN subcapsular lymphatic sinus induced proliferation of ovalbumin-specific, gut-tropic CD8(+) T cells in vivo. Finally, in 232-4 mice treated with R848, CD8α(+) LDCs were uniquely able to cross-prime interferon γ-producing CD8(+) T cells and drive their migration to the intestine. Our results clearly demonstrate that migrating CD8α(+) intestinal DCs are indispensable for cross-presentation of cellular antigens and, in conditions of inflammation, for the initial differentiation of effector CD8(+) T cells. They may therefore represent an important target for the development of antiviral vaccinations.Mucosal Immunology advance online publication, 21 May 2014; doi:10.1038/mi.2014.40.
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