scholarly journals Thymus-homing peripheral dendritic cells constitute two of the three major subsets of dendritic cells in the steady-state thymus

2009 ◽  
Vol 206 (3) ◽  
pp. 607-622 ◽  
Author(s):  
JiChu Li ◽  
JooHung Park ◽  
Deborah Foss ◽  
Irving Goldschneider
Keyword(s):  
Dendritic Cells ◽  
Normal Mouse ◽  
Regulatory Protein ◽  
Developmental Studies ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Functional Implications ◽  
Circulating Antigen ◽  
Plasmacytoid Dcs ◽  
Major Histocompatibility Complex Ii

Many dendritic cells (DCs) in the normal mouse thymus are generated intrathymically from common T cell/DC progenitors. However, our previous work suggested that at least 50% of thymic DCs originate independently of these progenitors. We now formally demonstrate by parabiotic, adoptive transfer, and developmental studies that two of the three major subsets of thymic DCs originate extrathymically and continually migrate to the thymus, where they occupy a finite number of microenvironmental niches. The thymus-homing DCs consisted of immature plasmacytoid DCs (pDCs) and the signal regulatory protein α–positive (Sirpα+) CD11b+ CD8α− subset of conventional DCs (cDCs), both of which could take up and transport circulating antigen to the thymus. The cDCs of intrathymic origin were mostly Sirpα− CD11b− CD8αhi cells. Upon arrival in the thymus, the migrant pDCs enlarged and up-regulated CD11c, major histocompatibility complex II (MHC II), and CD8α, but maintained their plasmacytoid morphology. In contrast, the migrant cDCs proliferated extensively, up-regulated CD11c, MHC II, and CD86, and expressed dendritic processes. The possible functional implications of these findings are discussed.

scholarly journals High Levels of a Major Histocompatibility Complex II–Self Peptide Complex on Dendritic Cells from the T Cell Areas of Lymph Nodes

1997 ◽  
Vol 186 (5) ◽  
pp. 665-672 ◽  
Author(s):  
Kayo Inaba ◽  
Maggie Pack ◽  
Muneo Inaba ◽  
Hiraki Sakuta ◽  
Frank Isdell ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Mhc I ◽  
Peptide Complex ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Peripheral Lymph ◽  
Free Media ◽  
Very High

T lymphocytes recirculate continually through the T cell areas of peripheral lymph nodes. During each passage, the T cells survey the surface of large dendritic cells (DCs), also known as interdigitating cells. However, these DCs have been difficult to release from the lymph node. By emphasizing the use of calcium-free media, as shown by Vremec et al. (Vremec, D., M. Zorbas, R. Scollay, D.J. Saunders, C.F. Ardavin, L. Wu, and K. Shortman. 1992. J. Exp. Med. 176:47–58.), we have been able to release and enrich DCs from the T cell areas. The DCs express the CD11c leukocyte integrin, the DEC-205 multilectin receptor for antigen presentation, the intracellular granule antigens which are recognized by monoclonal antibodies M342, 2A1, and MIDC-8, very high levels of MHC I and MHC II, and abundant accessory molecules such as CD40, CD54, and CD86. When examined with the Y-Ae monoclonal which recognizes complexes formed between I-Ab and a peptide derived from I-Eα, the T cell area DCs expressed the highest levels. The enriched DCs also stimulated a T-T hybridoma specific for this MHC II–peptide complex, and the hybridoma underwent apoptosis. Therefore DCs within the T cell areas can be isolated. Because they present very high levels of self peptides, these DCs should be considered in the regulation of self reactivity in the periphery.

scholarly journals Dendritic Cells Inhibit the Progression of Listeria monocytogenes Intracellular Infection by Retaining Bacteria in Major Histocompatibility Complex Class II-Rich Phagosomes and by Limiting Cytosolic Growth

2010 ◽  
Vol 78 (7) ◽  
pp. 2956-2965 ◽  
Author(s):  
Marlena M. Westcott ◽  
Curtis J. Henry ◽  
Jacqueline E. Amis ◽  
Elizabeth M. Hiltbold
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Listeria Monocytogenes ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex

ABSTRACT Dendritic cells (DC) provide a suboptimal niche for the growth of Listeria monocytogenes, a facultative intracellular bacterial pathogen of immunocompromised and pregnant hosts. This is due in part to a failure of large numbers of bacteria to escape to the cytosol, an essential step in the intracellular life cycle that is mediated by listeriolysin O (LLO). Here, we demonstrate that wild-type bacteria that failed to enter the cytosol of bone marrow-derived DC were retained in a LAMP2+ compartment. An isogenic L. monocytogenes strain that produces an LLO protein with reduced pore-forming activity had a severe escape and growth phenotype in DC. Few mutant bacteria entered the cytosol in the first 2 h and were instead found in LAMP2+, major histocompatibility complex class II+ (MHC-II+) H2-DM vesicles characteristic of MHC-II antigen loading compartments (MIIC). In contrast, the mutant had a minor phenotype in bone marrow-derived macrophages (BMM) despite the reduced LLO activity. In the first hour, DC phagosomes acidified to a pH that was, on average, half a point higher than that of BMM phagosomes. Unlike BMM, L. monocytogenes growth in DC was minimal after 5 h, and consequently, DC remained viable and matured late in infection. Taken together, the data are consistent with a model in which phagosomal maturation events associated with the acquisition of MHC-II molecules present a suboptimal environment for L. monocytogenes escape to the DC cytosol, possibly by limiting the activity of LLO. This, in combination with an undefined mechanism that controls bacterial growth late in infection, promotes DC survival during the critical maturation response.

PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells

Blood ◽  
2000 ◽  
Vol 95 (3) ◽  
pp. 879-885 ◽  
Author(s):  
Anastasia Guerriero ◽  
Peter B. Langmuir ◽  
Lisa M. Spain ◽  
Edward W. Scott
Keyword(s):  
Dendritic Cells ◽  
Interleukin 4 ◽  
Low Density ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Ets Family ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Mixed Lymphocyte Reactions

The ets-family transcription factor PU.1 is required for the proper development of both myeloid and lymphoid progenitors. We used PU.1-deficient animals to examine the role of PU.1 during dendritic cell development. PU.1−/−animals produce lymphoid-derived dendritic cells (DC): low-density class II major histocompatibility complex [MHC-II+] CD11c+ CD8+DEC-205+. But they lack myeloid-derived DC: low-density MHC-II+ CD11c+ CD8−DEC-205−. PU.1−/− embryos also lack progenitors capable of differentiating into myeloid DC in response to granulocyte-macrophage colony-stimulating factor plus interleukin-4. The appearance of lymphoid DC in developing PU.1−/−thymus was initially delayed, but this population recovered to wild type (WT) levels upon organ culture of isolated thymic lobes. PU.1−/−lymphoid DC were functionally equivalent to WT DC for stimulating T-cell proliferation in mixed lymphocyte reactions. These results demonstrate that PU.1 is required for the development of myeloid DC but not lymphoid DC.

scholarly journals Immunodetection of myeloid and plasmacytoid dendritic cells in mammary carcinomas of female dogs

2015 ◽  
Vol 35 (11) ◽  
pp. 906-912
Author(s):  
Mayara C. Rosolem ◽  
Rosemeri O. Vasconcelos ◽  
Eduardo Garrido ◽  
Thaís L.L. Castanheira ◽  
Pamela R.R. Moreira ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Cells ◽  
Mammary Tissue ◽  
Control Group ◽  
Simple Type ◽  
Mammary Carcinomas ◽  
Mhc Ii ◽  
Tumor Group ◽  
Significant Difference ◽  
Plasmacytoid Dcs

ABSTRACT: Dendritic cells have attracted great interest from researchers as they may be used as targets of tumor immune evasion mechanisms. The main objective of this study was to evaluate the relationship between the dendritic cells (DCs) subpopulation in simple type mammary carcinomas in female dogs. Two groups of samples were used: the control group consisted of 18 samples of mammary tissue without changes and the tumor group with 26 simple type mammary carcinomas. In these groups, we evaluated the immunodetection of immature and mature myeloid DCs, plasmacytoid DCs and MHC-II. In mammary tumor, mature myeloid DCs predominated in the peritumoral region, while immature myeloid DCs and plasmacytoid DCs were evident in the intratumoral region. Immunostaining of MHC-II was visualized in mammary acini (control group), in tumor cells and inflammatory infiltration associated with tumors. The comparison between the control and tumor groups showed a statistically significant difference between immature myeloid DCs, mature myeloid DCs and plasmacytoid DCs. The immunodetection of MHC-II was not significant when comparing the groups. The predominance of immature DCs in the tumor group is possibly related to an inefficient immune response, promoting the development and survival of tumor cells. The presence of plasmacytoid DCs in the same group suggests a worse prognosis for female dogs with mammary tumors. Therefore, the ability of differentiation of canine dendritic cells could be influenced by neoplastic cells and by the tumor microenvironment.

scholarly journals Decellularized Lymph Node Scaffolding as a Carrier for Dendritic Cells to Induce Anti-Tumor Immunity

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 553 ◽  
Author(s):  
Hung-Jun Lin ◽  
Weu Wang ◽  
Yi-You Huang ◽  
Wei-Tsen Liao ◽  
Ting-Yu Lin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
Antitumor Immunity ◽  
Cpg Oligodeoxynucleotides ◽  
Mhc Ii ◽  
Decellularized Extracellular Matrix ◽  
Histocompatibility Complex ◽  
Ecm Architecture ◽  
In Vivo Delivery

In recent decades, the decellularized extracellular matrix (ECM) has shown potential as a promising scaffold for tissue regeneration. In this study, an organic acid decellularized lymph node (dLN) was developed as a carrier for dendritic cells (DCs) to induce antitumor immunity. The dLNs were prepared by formic acid, acetic acid, or citric acid treatment. The results showed highly efficient removal of cell debris from the lymph node and great preservation of ECM architecture and biomolecules. In addition, bone marrow dendritic cells (BMDCs) grown preferably inside the dLN displayed the maturation markers CD80, CD86, and major histocompatibility complex (MHC)-II, and they produced high levels of interleukin (IL)-1β, IL-6, and IL-12 cytokines when stimulated with ovalbumin (OVA) and CpG oligodeoxynucleotides (CPG-ODN). In an animal model, the BMDC-dLN completely rejected the E.G7-OVA tumor. Furthermore, the splenocytes from BMDC-dLN-immunized mice produced more interferon gamma, IL-4, IL-6, and IL-2, and they had a higher proliferation rate than other groups when re-stimulated with OVA. Hence, BMDC-dLN could be a promising DC-based scaffold for in vivo delivery to induce potent antitumor immunity.

scholarly journals Phosphatidylinositol-4-kinase IIα licenses phagosomes for TLR4 signaling and MHC-II presentation in dendritic cells

2020 ◽  
Vol 117 (45) ◽  
pp. 28251-28262
Author(s):  
Cynthia López-Haber ◽  
Roni Levin-Konigsberg ◽  
Yueyao Zhu ◽  
Jing Bi-Karchin ◽  
Tamas Balla ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Adaptor Protein ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Tlr Signaling ◽  
Tubule Formation ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Phosphatidylinositol 4 ◽  
Phagosomal Membrane

Toll-like receptor (TLR) recruitment to phagosomes in dendritic cells (DCs) and downstream TLR signaling are essential to initiate antimicrobial immune responses. However, the mechanisms underlying TLR localization to phagosomes are poorly characterized. We show herein that phosphatidylinositol-4-kinase IIα (PI4KIIα) plays a key role in initiating phagosomal TLR4 responses in murine DCs by generating a phosphatidylinositol-4-phosphate (PtdIns4P) platform conducive to the binding of the TLR sorting adaptor Toll-IL1 receptor (TIR) domain-containing adaptor protein (TIRAP). PI4KIIα is recruited to maturing lipopolysaccharide (LPS)-containing phagosomes in an adaptor protein-3 (AP-3)-dependent manner, and both PI4KIIα and PtdIns4P are detected on phagosomal membrane tubules. Knockdown of PI4KIIα—but not the related PI4KIIβ—impairs TIRAP and TLR4 localization to phagosomes, reduces proinflammatory cytokine secretion, abolishes phagosomal tubule formation, and impairs major histocompatibility complex II (MHC-II) presentation. Phagosomal TLR responses in PI4KIIα-deficient DCs are restored by reexpression of wild-type PI4KIIα, but not of variants lacking kinase activity or AP-3 binding. Our data indicate that PI4KIIα is an essential regulator of phagosomal TLR signaling in DCs by ensuring optimal TIRAP recruitment to phagosomes.

scholarly journals Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells

2010 ◽  
Vol 207 (6) ◽  
pp. 1273-1281 ◽  
Author(s):  
Annabell Bachem ◽  
Steffen Güttler ◽  
Evelyn Hartung ◽  
Frédéric Ebstein ◽  
Michael Schaefer ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Human Blood ◽  
Low Frequency ◽  
Cross Presentation ◽  
Functional Studies ◽  
Histocompatibility Complex ◽  
Plasmacytoid Dcs ◽  
Human Dendritic Cells ◽  
Specific Ligand

In recent years, human dendritic cells (DCs) could be subdivided into CD304+ plasmacytoid DCs (pDCs) and conventional DCs (cDCs), the latter encompassing the CD1c+, CD16+, and CD141+ DC subsets. To date, the low frequency of these DCs in human blood has essentially prevented functional studies defining their specific contribution to antigen presentation. We have established a protocol for an effective isolation of pDC and cDC subsets to high purity. Using this approach, we show that CD141+ DCs are the only cells in human blood that express the chemokine receptor XCR1 and respond to the specific ligand XCL1 by Ca2+ mobilization and potent chemotaxis. More importantly, we demonstrate that CD141+ DCs excel in cross-presentation of soluble or cell-associated antigen to CD8+ T cells when directly compared with CD1c+ DCs, CD16+ DCs, and pDCs from the same donors. Both in their functional XCR1 expression and their effective processing and presentation of exogenous antigen in the context of major histocompatibility complex class I, human CD141+ DCs correspond to mouse CD8+ DCs, a subset known for superior antigen cross-presentation in vivo. These data define CD141+ DCs as professional antigen cross-presenting DCs in the human.

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