In Vivo Antigen Presentation Capacity of Dendritic Cells from Oral Mucosa and Skin Draining Lymph Nodes

1994 ◽  
pp. 63-67 ◽  
Author(s):  
Erna van Wilsem ◽  
Ingrid van Hoogstraten ◽  
John Brevé ◽  
Yaved Zaman ◽  
Georg Kraal
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Antigen Presentation ◽  
Oral Mucosa ◽  
Draining Lymph Nodes

scholarly journals Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity

2021 ◽  
Vol 118 (3) ◽  
pp. e2021364118
Author(s):  
Hannah L. Miller ◽  
Prabhakar Sairam Andhey ◽  
Melissa K. Swiecki ◽  
Bruce A. Rosa ◽  
Konstantin Zaitsev ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Diphtheria Toxin ◽  
Fluorescein Isothiocyanate ◽  
Skin Inflammation ◽  
Contact Hypersensitivity ◽  
Type I ◽  
Th2 Response ◽  
Draining Lymph Nodes

Plasmacytoid dendritic cells (pDCs) specialize in the production of type I IFN (IFN-I). pDCs can be depleted in vivo by injecting diphtheria toxin (DT) in a mouse in which pDCs express a diphtheria toxin receptor (DTR) transgene driven by the human CLEC4C promoter. This promoter is enriched for binding sites for TCF4, a transcription factor that promotes pDC differentiation and expression of pDC markers, including CLEC4C. Here, we found that injection of DT in CLEC4C-DTR+ mice markedly augmented Th2-dependent skin inflammation in a model of contact hypersensitivity (CHS) induced by the hapten fluorescein isothiocyanate. Unexpectedly, this biased Th2 response was independent of reduced IFN-I accompanying pDC depletion. In fact, DT treatment altered the representation of conventional dendritic cells (cDCs) in the skin-draining lymph nodes during the sensitization phase of CHS; there were fewer Th1-priming CD326+ CD103+ cDC1 and more Th2-priming CD11b+ cDC2. Single-cell RNA-sequencing of CLEC4C-DTR+ cDCs revealed that CD326+ DCs, like pDCs, expressed DTR and were depleted together with pDCs by DT treatment. Since CD326+ DCs did not express Tcf4, DTR expression might be driven by yet-undefined transcription factors activating the CLEC4C promoter. These results demonstrate that altered DC representation in the skin-draining lymph nodes during sensitization to allergens can cause Th2-driven CHS.

Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS

Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 2859-2868 ◽  
Author(s):  
Michael I. Zimmer ◽  
Adriana T. Larregina ◽  
Cielo M. Castillo ◽  
Saverio Capuano ◽  
Louis D. Falo ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Langerhans Cells ◽  
Receptor Expression ◽  
Peripheral Tissues ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Draining Lymph Nodes

Abstract Langerhans cells (LCs) are immature dendritic cells (DCs) that capture antigen in peripheral tissues and migrate to draining lymph nodes, where they reside in the paracortex as interdigitating dendritic cells (IDCs). We studied the effects of simian immunodeficiency virus (SIV) on LCs and IDCs during different stages of infection in monkeys. LCs isolated from monkeys with acute SIV infection or acquired immunodeficiency syndrome (AIDS) underwent normal maturation in vitro, including a switch in chemokine receptor expression from CCR5 to CXCR4 and CCR7. LCs migrated normally from skin in response to contact sensitization in monkeys with acute SIV infection. In contrast, LC migration from skin was markedly impaired during AIDS, associated with a reduction in antigen-bearing DCs in draining lymph nodes. Lymph node IDCs were increased in proportion during acute SIV infection and had an activated phenotype, whereas during AIDS IDCs had significantly lower expression of CD40 and the activation marker CD83. IDCs from monkeys with AIDS were refractory to stimulation with CD40L, demonstrating a functional consequence of decreased CD40 expression. SIV-infected DCs were not identified in lymph nodes or skin of monkeys with AIDS, suggesting an indirect effect of infection on DC populations in vivo. These data indicate that DCs are mobilized to lymph nodes during acute SIV infection, but that during AIDS this process is suppressed, with LC migration and IDC activation being impaired. We conclude that disruption of DC homeostasis may play a role in immunopathology induced by human immunodeficiency virus and suggest that therapeutic strategies targeting DCs may have limited efficacy during AIDS.

scholarly journals Trance, a Tumor Necrosis Factor Family Member, Enhances the Longevity and Adjuvant Properties of Dendritic Cells in Vivo

2000 ◽  
Vol 191 (3) ◽  
pp. 495-502 ◽  
Author(s):  
Régis Josien ◽  
Hong-Li Li ◽  
Elizabeth Ingulli ◽  
Supria Sarma ◽  
Brian R.Wong ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Lymph Nodes ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
T Cell Priming ◽  
Draining Lymph Nodes ◽  
Necrosis Factor

Mature dendritic cells (DCs) are powerful antigen presenting cells that have the unique capacity to migrate to the T cell zone of draining lymph nodes after subcutaneous injection. Here we report that treatment of antigen-pulsed mature DCs with tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE), a TNF family member, before immunization enhances their adjuvant capacity and elicits improved T cell priming in vivo, such that both primary and memory T cell immune responses are enhanced. By enumerating migratory DCs in the draining lymph nodes and by studying their function in stimulating naive T cells, we show that one of the underlying mechanisms for enhanced T cell responses is an increase in the number of ex vivo antigen-pulsed DCs that are found in the T cell areas of lymph nodes. These results suggest that the longevity and abundance of mature DCs at the site of T cell priming influence the strength of the DC-initiated T cell immunity in situ. Our findings have the potential to improve DC-based immunotherapy; i.e., the active immunization of humans with autologous DCs that have been pulsed with clinically significant antigens ex vivo.

scholarly journals In vivo two-photon imaging of T cell motility in joint-draining lymph nodes in a mouse model of rheumatoid arthritis

2012 ◽  
Vol 278 (1-2) ◽  
pp. 158-165 ◽  
Author(s):  
Tamás Kobezda ◽  
Sheida Ghassemi-Nejad ◽  
Tibor T. Glant ◽  
Katalin Mikecz
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Mouse Model ◽  
Lymph Nodes ◽  
Cell Motility ◽  
Two Photon ◽  
Photon Imaging ◽  
Two Photon Imaging ◽  
Draining Lymph Nodes

scholarly journals In Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells

Immunity ◽  
2010 ◽  
Vol 32 (2) ◽  
pp. 227-239 ◽  
Author(s):  
Heung Kyu Lee ◽  
Lisa M. Mattei ◽  
Benjamin E. Steinberg ◽  
Philipp Alberts ◽  
Yun Hee Lee ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antigen Presentation

scholarly journals Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo

2014 ◽  
Vol 211 (8) ◽  
pp. 1657-1672 ◽  
Author(s):  
Derek K. Chu ◽  
Rodrigo Jimenez-Saiz ◽  
Christopher P. Verschoor ◽  
Tina D. Walker ◽  
Susanna Goncharova ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Eosinophil Peroxidase ◽  
Th2 Immune Response ◽  
Intestinal Immune System ◽  
Eosinophil Activation ◽  
And Migration ◽  
Deficient Mice ◽  
Draining Lymph Nodes

Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. Eosinophils controlled CD103+ dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.

scholarly journals PGE2-induced metalloproteinase-9 is essential for dendritic cell migration

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 260-270 ◽  
Author(s):  
Jui-Hung Yen ◽  
Tanzilya Khayrullina ◽  
Doina Ganea
Keyword(s):  
Lymph Nodes ◽  
Basement Membranes ◽  
Directional Migration ◽  
Dendritic Cell Migration ◽  
Membrane Bound ◽  
Induced Changes ◽  
Expression Program ◽  
Metalloproteinase 9 ◽  
Draining Lymph Nodes

Following antigen acquisition and maturation, dendritic cells (DCs) disengage from the extracellular matrix, cross basement membranes, and travel to draining lymph nodes to activate T cells. CCR7 expression is necessary but not sufficient for the directional migration of DCs. Prostaglandin E2 (PGE2), present in inflammatory sites, induces DC migration, presumably by enacting a migration-permissive gene expression program. Since regulation of DC migration is highly important for their use in vaccination and therapy, we examined the PGE2-induced changes in the expression of metalloproteinases (MMPs). Our results indicate that PGE2 significantly up-regulates MMP-9 expression, induces both secreted and membrane-bound MMP-9, and that in turn, DC-derived MMP-9 is essential for DC chemotaxis in response to the CCR7 ligand CCL19, Matrigel migration, and in vivo migration in both wild-type and MMP-9–deficient hosts. We conclude that DCs matured within inflammatory sites require both CCR7 and PGE2-induced MMP-9 for their directional migration to draining lymph nodes.

scholarly journals Activation-induced cell death of self-reactive regulatory T cells drives autoimmunity

2019 ◽  
Vol 116 (52) ◽  
pp. 26788-26797
Author(s):  
Ester Badami ◽  
Olivier N. F. Cexus ◽  
Sonia Quaratino
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Lymph Nodes ◽  
Autoimmune Thyroiditis ◽  
The Self ◽  
Thyroid Peroxidase ◽  
Activation Induced Cell Death ◽  
Self Antigen ◽  
Draining Lymph Nodes

Activation of self-reactive T cells is a major driver to autoimmunity and is suppressed by mechanisms of regulation. In a humanized model of autoimmune thyroiditis, we investigated the mechanism underlying break of tolerance. Here, we found that a human TCR specific for the self-antigen thyroid peroxidase (TPO) is positively selected in the thymus of RAG KO mice on both T effector (Teff) and T regulatory (Treg) CD4+Foxp3+cells. In vivo Teffare present in all immune organs, whereas the TPO-specific Tregare present in all lymphoid organs with the exception of the thyroid-draining lymph nodes. We suggest that the presence of TPO in the thyroid draining lymph nodes induces the activation of Teffand the depletion of Tregvia activation-induced cell death (AICD). Our findings provide insights on the failure of the mechanisms of immune tolerance, with potential implications in designing immunotherapeutic strategies.

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