Downregulation of MHC Class II by Ubiquitination Is Required for the Migration of CD206+ Dendritic Cells to Skin-Draining Lymph Nodes

Abstract. Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20–30% were seen in contact with now-present intrathyroidal T-helper lymphocytes. The so-formed lymphoid cell aggregates were predominantly small (< 10 cells), but very large aggregates could also be detected. These large accumulations were highly organized and composed of T-cell zones, B-cell zones and numerous plasma cells. Such accumulations are reminiscent of secondary lymphoid organs. In view of these morphological data it is conceivable that thyroid dendritic cells are of prime importance in the presentation of autoantigen in thyroid autoimmune disease. Throughout the process of autosensitization in the BB/W rat thyroid epithelial cells stayed negative for Class II MHC determinants. This shows that Class II expression on thyrocytes is not prerequisite for thyroid autoimmunity to develop.

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Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b+ dendritic cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1513532112 ◽

2015 ◽

Vol 112 (41) ◽

pp. 12782-12787 ◽

Cited By ~ 30

Author(s):

Jonathan L. Linehan ◽

Thamotharampillai Dileepan ◽

Sakeen W. Kashem ◽

Daniel H. Kaplan ◽

Patrick Cleary ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Lymph Nodes ◽

Mhc Class Ii ◽

Th17 Cells ◽

Cell Subset ◽

Class Ii ◽

Dendritic Cell Subset ◽

Cervical Lymph Nodes ◽

Tgf Β1

Intranasal (i.n.) infections preferentially generate Th17 cells. We explored the basis for this anatomic preference by tracking polyclonal CD4+ T cells specific for an MHC class II-bound peptide from the mucosal pathogen Streptococcus pyogenes. S. pyogenes MHC class II-bound peptide-specific CD4+ T cells were first activated in the cervical lymph nodes following i.n. inoculation and then differentiated into Th17 cells. S. pyogenes-induced Th17 formation depended on TGF-β1 from dendritic cells and IL-6 from a CD301b+ dendritic cell subset located in the cervical lymph nodes but not the spleen. Thus, the tendency of i.n. infection to induce Th17 cells is related to cytokine production by specialized dendritic cells that drain this site.

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Draining Lymph Nodes of Corneal Transplant Hosts Exhibit Evidence for Donor Major Histocompatibility Complex (MHC) Class II–positive Dendritic Cells Derived from MHC Class II–negative Grafts

Journal of Experimental Medicine ◽

10.1084/jem.20010838 ◽

2002 ◽

Vol 195 (2) ◽

pp. 259-268 ◽

Cited By ~ 133

Author(s):

Ying Liu ◽

Pedram Hamrah ◽

Qiang Zhang ◽

Andrew W. Taylor ◽

M. Reza Dana

Keyword(s):

Dendritic Cells ◽

Major Histocompatibility Complex ◽

Lymph Nodes ◽

Mhc Class Ii ◽

Fluorescent Protein ◽

Class Ii ◽

Corneal Transplant ◽

Dependent Manner ◽

Major Histocompatibility ◽

Histocompatibility Complex

To examine the widely accepted dogmas that corneal grafts lack passenger leukocytes or cells capable of migrating directly to lymph nodes (LNs), we tracked the migration of corneal graft-derived transgenic green fluorescent protein (GFP; Iab) cells into the draining LNs of allogeneic (Iad) recipients. GFP+ cells were identified in cervical LNs several hours after transplantation, and this traffic was significantly enhanced when grafts were placed in inflamed recipient beds. Draining cells were Iab+, CD45+, and CD11c+, and examination of ungrafted corneas revealed numerous similarly CD45+CD11c+CD3−CD8α− cells that uniformly lacked major histocompatibility complex (MHC) class II expression; transmission electron microscopy confirmed the presence of morphologically similar cells. After transplantation, or placement in culture, these CD11c+ cells became class II+ in a time-dependent manner and were capable of allostimulatory function. However, the stimulatory capacity of these cornea-derived dendritic cells (DCs) was suppressed compared with splenic controls. These results demonstrate for the first time that the cornea is endowed with resident DCs that are universally MHC class II− but that are capable of expressing class II antigen after surgery and migrating to draining LNs of allografted hosts. These data refute the tenet that the cornea is immune privileged due to lack of resident lymphoreticular cells or due to antigenic sequestration from systemic immunity.

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