Enteric bacterial antigens activate CD4+ T cells fromscid mice with inflammatory bowel disease

Brimnes, Jens; Reimann, Jörg; Nissen, Mogens Holst; Claësson, Mogens H.

doi:10.1002/1521-4141(200101)31:1<23::aid-immu23>3.0.co;2-2

Cited by 83 publications

(73 citation statements)

References 37 publications

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“…The small number of memory/effector cells transplanted and the diverse TCR V␤ repertoire of CD4 ϩ T cell populations recovered from the inflamed cLP (Z Trobonjaca, unpublished data) suggest that CD4 ϩ T cells are primed to gut-derived antigens in the adoptive host. The data in Figure 5 show that CD4 ϩ T cells specifically react to gut-derived antigens presented by DC, confirming and extending our previous report (Brimnes et al, 2001). This leads to the question of where CD4 ϩ T cells are primed in the adoptive host.…”

Section: Dendritic Cell Aggregates In Early Colitissupporting

confidence: 90%

Clustering of Colonic Lamina Propria CD4+ T Cells to Subepithelial Dendritic Cell Aggregates Precedes the Development of Colitis in a Murine Adoptive Transfer Model

Leithäuser

Trobonjača

Möller

et al. 2001

Laboratory Investigation

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SUMMARY: Initial lesions in inflammatory bowel disease induced during the repopulation of immunodeficient RAG1-/-mice with immunocompetent CD4 ϩ T cells have not been previously described. In this transfer colitis model, we followed CD4 ϩ T cell repopulation in the host by injecting autofluorescent CD4 ϩ T cells from congenic, enhanced green fluorescent protein (eGFP)-transgenic mice. This allowed the direct, sensitive, and unambiguous histological detection of the repopulation of the intestinal tract, mesenteric lymph nodes, and spleen of the host with donor eGFP ϩ CD4 ϩ T cells. We identified in RAG1 -/-mice intestinal dendritic cell (DC) aggregates under the basal crypt epithelium at the mucosa/submucosa junction from which F4/80 ϩ macrophages were excluded. At Days 8 to 11 posttransfer (before colitis was manifest), CD4 ϩ T cells clustered and proliferated in CD11c ϩ DC aggregates. T cell clustering was most pronounced in the cecum where histologically overt colitis became manifest 5 to 10 days later. Junctional DC aggregates were thus prevalent in the triggering phase of the disease. The data suggest that pathogenic T cell responses inducing inflammatory bowel disease are primed or restimulated in situ in junctional CD4 ϩ T cell/DC aggregates. (Lab Invest 2001, 81:1339 -1349.

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Section: Dendritic Cell Aggregates In Early Colitissupporting

confidence: 90%

Clustering of Colonic Lamina Propria CD4+ T Cells to Subepithelial Dendritic Cell Aggregates Precedes the Development of Colitis in a Murine Adoptive Transfer Model

Leithäuser

Trobonjača

Möller

et al. 2001

Laboratory Investigation

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“…CD4 1 T cells transferred into immune-deficient mice lead to IBD in response to enteric bacterial antigens derived from commensal microorganism, causing lethal weight loss and diarrhea due to endothelial and crypt hyperplasia as well as significant accumulation of lymphocytes, neutrophils, and macrophages within the lamina propria in the large intestine. 31,[59][60][61][62] In most human and mouse cases examined, IBD is associated with Th1-producing TNF and IFN-c, which are important mediators of this disease. 63,64 Th17 cells also have been suggested to play a key role in the pathogenesis of colitis and IBD, as they convert into Th1 cells and promote Th1 responses through IL-12 and IL-23.…”

Section: Discussionmentioning

confidence: 99%

CD4+VEGFR1HIGH T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice

et al. 2015

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Regulatory T cells (Tregs) are a specialized subpopulation of T cells that control the immune response and thereby maintain immune system homeostasis and tolerance to self-antigens. Many subsets of CD4 1 Tregs have been identified, including Foxp3 1 , Tr1, Th3, and Foxp3neg iT(R)35 cells. In this study, we identified a new subset of CD4 1 VEGFR1 high Tregs that have immunosuppressive capacity. CD4 1 VEGFR1high T cells, which constitute approximately 1.0% of CD4 1 T cells, are hyporesponsive to T-cell antigen receptor stimulation. Surface marker and FoxP3 expression analysis revealed that CD4 1 VEGFR1 high T cells are distinct from known Tregs. CD4 1 VEGFR1 high T cells suppressed the proliferation of CD4 1 CD25 2 T cell as efficiently as CD4 1 CD25 high natural Tregs in a contact-independent manner. Furthermore, adoptive transfer of CD4 1 VEGFR1 1 T cells from wild type to RAG-2-deficient C57BL/6 mice inhibited effector T-cell-mediated inflammatory bowel disease. Thus, we report CD4 1 VEGFR1 high T cells as a novel subset of Tregs that regulate the inflammatory response in the intestinal tract.

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“…In some experiments, target lymphocytes were washed and fluorescently labeled with CFSE using the Vybrant CFDA SE Cell Tracer kit (Molecular Probes). In specified cocultures, intestinal Ag was provided in the form of sterile fecal extract (200 g of protein/ml) (13). Apoptosis pathways were blocked with a general caspase inhibitor (20 M, Z-VAD-FMK; Promega); an inactive peptide was used as a control for caspase inhibition (20 M, Z-FA-FMK).…”

Section: Coculturesmentioning

confidence: 99%

Macrophages Driven to a Novel State of Activation Have Anti-Inflammatory Properties in Mice

Brem‐Exner

Sattler²,

Hutchinson

et al. 2008

The Journal of Immunology

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Recurrent episodes of inflammation underlie numerous pathologies, notably those of inflammatory bowel diseases. In this study, we describe a population of macrophages in a novel state of activation that mitigates colitis in mice. The cells responsible for this effect, called IFN-γ-stimulated monocyte-derived cells (IFNγ-MdC), derive from mouse spleen, blood, and bone marrow monocytes and are distinguished from known macrophage populations by mode of generation, cell surface phenotype, and function. IFNγ-MdC only arise when macrophages are cultivated in the presence of CD40L-expressing CD4+ T cells, M-CSF, and IFN-γ. IFNγ-MdC express markers including F4/80, CD11b/c, CD86, and CD274; they are negative for CD4, CD8, Gr1, CD19, CD80, and CD207. Functionally, IFNγ-MdC are defined by their capacity to enrich cocultured T cell populations for CD4+CD25+Foxp3+ regulatory cells; this enrichment, constituting up to 60% or more of residual lymphocytes, is attributed to an expansion, but also to a cell contact and caspase-dependent depletion of activated T cells. In mice, IFNγ-MdC delivered i.v. traffic to gut-associated peripheral lymphoid tissues, including the mesenteric lymph nodes, Peyer’s patches, and colonic mucosa, and promote the clinical and histological resolution of chronic colitis. We conclude that IFNγ-MdC represent macrophages in a novel state of activation, possessing multiple T cell-suppressive effects with therapeutic potential for the treatment of autoimmune inflammation.

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Enteric bacterial antigens activate CD4+ T cells fromscid mice with inflammatory bowel disease

Cited by 83 publications

References 37 publications

Clustering of Colonic Lamina Propria CD4+ T Cells to Subepithelial Dendritic Cell Aggregates Precedes the Development of Colitis in a Murine Adoptive Transfer Model

Clustering of Colonic Lamina Propria CD4+ T Cells to Subepithelial Dendritic Cell Aggregates Precedes the Development of Colitis in a Murine Adoptive Transfer Model

CD4+VEGFR1HIGH T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice

Macrophages Driven to a Novel State of Activation Have Anti-Inflammatory Properties in Mice

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