A Discrete Subpopulation of Dendritic Cells Transports Apoptotic Intestinal Epithelial Cells to T Cell Areas of Mesenteric Lymph Nodes

By F. Huang, N. Platt, M. Wykes, J. Major, T. Powell, Chris Jenkins, G. MacPherson. Journal of Experimental Medicine, 2000

992 citations recorded by the source corpus.

This study identifies a dendritic cell (DC) subset that constitutively transports apoptotic intestinal epithelial cell remnants to T cell areas of mesenteric lymph nodes in vivo. Rat intestinal lymph contains two DC populations. Both populations have typical DC morphology, are major histocompatibility complex class IIhi, and express OX62, CD11c, and B7. CD4+/OX41+ DCs are strong antigen-presenting cells (APCs). CD4−/OX41− DCs are weak APCs and contain cytoplasmic apoptotic DNA, epithelial cell–restricted cytokeratins, and nonspecific esterase (NSE)+ inclusions, not seen in OX41+ DCs. Identical patterns of NSE electrophoretic variants exist in CD4−/OX41− DCs, intestinal epithelial cells, and mesenteric node DCs but not in other DC populations, macrophages, or tissues. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick-end labeling (TUNEL)-positive DCs and strongly NSE+ DCs are present in intestinal lamina propria. Peyer's patches and mesenteric but not other lymph nodes contain many strongly NSE+ DCs in interfollicular and T cell areas. Similar DCs are seen in the ileum and in T cell areas of mesenteric nodes in gnotobiotic rats. These results show that a distinct DC subset constitutively endocytoses and transports apoptotic cells to T cell areas and suggest a role for these DCs in inducing and maintaining peripheral self-tolerance.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/63b9054eb3551f60f989da1e7ae2fd5b2e053ba8

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Citations in the corpus

Dendritic cells: specialized and regulated antigen processing machines. (2001, background): “The maturing DCs also well as self antigens derived from tissues exhibiting consti- upregulate the capacity to generate functional peptidetutive cell turnover (Huang et al., 2000).”
A blast from the past: clearance of apoptotic cells regulates immune responses (2002, background): “However, there is circumstantial evidence that DC-mediated uptake and presentation of self-components packaged in apoptotic cells might reinforce peripheral tolerance by inducing anergy or deletion of T cell”
Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement (2006, background): “We have not yet been able to follow a DC with an internal microbial load leaving its sub-epithelial position and entering a lymphatic for migration to a local lymph node (44), migrating to a nearby Payer’s patch to initiate a response in this site (45–48), or interacting with a memory T cell within ”
Adhesion mechanisms regulating the migration of monocytes (2004, background): “A few reports indicate that DCs are able to transport apoptotic cells or self-antigens from the periphery to the lymph nodes, in the absence of an exogenous stimulu”
Dendritic cells: translating innate to adaptive immunity. (2006, background): “mesenteric lymph, a subset of DCs contain apoptotic bodies, earlier termed DNA positive inclusions [31]; these cells also can be marked for the keratins and nonspecific esterases of the intestinal epithelium [47].”
Antigen-Specific Inhibition of Effector T Cell Function in Humans after Injection of Immature Dendritic Cells (2001, positive): “, phagocytosed apoptotic cells) might elicit tolerance to naive peripheral T cells in vivo (10, 11).”
Regulation of T cell immunity by dendritic cells. (2001, background): “Immature DCs possess high levels of constitutive macropino- bodies taken up in peripheral tissues (Huang et al., 2000).”
The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo (2002, background): “who have reported that the subset of CD4 DCs in rat mesenteric lymph selectively carries apoptotic fragments of intestinal epithelial cells (40).”
Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo (2007, background): “The lymph nodes of mice or rats that are maintained in germ-free condition”
Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria (2001, background): “Among CD18 + cells, dendritic cells (DCs) are migratory and phagocytic cells that are ideally located for antigen sampling in tissues that interface with the external environment, such as skin and mucosae, where they perform a sentinel function for incoming pathogen”
Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor α Induce Antigen-specific Protection of Mice from Autoimmunity (2002, background): “The in vivo counterparts that most closely resemble our in vitro generated TNF/DCs are the “veiled cells” of the lymphatics, which migrate to the peripheral lymph nodes transporting tissue antigens (30) or apoptotic cells (31) and there finally represent a distinguishable subset of skin derived DC (”