Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow.

Thyroid-stimulating hormone (TSH), a central neuroendocrine mediator of the hypothalamus-pituitary-thyroid axis, has been shown to affect various aspects of immunological development and function. To gain a better understanding of TSH involvement within the mammalian immune system, the expression and distribution of the TSH receptor (TSHr) has been studied by immunoprecipitation and by flow cytometric analyses. Using highly enriched populations of B cells, T cells, and dendritic cells, trace amounts of TSHr were precipitated from B cells and T cells, whereas high levels of TSHr were precipitated from the dendritic cell fraction. Flow cytometric analyses of TSHr expression on splenic and lymph node T cells revealed a major difference between those tissues in that only 2–3% of splenic T cells were TSHr+, whereas 10–20% of CD4+8− and CD4−8+ lymph node T cells expressed the TSHr, which was exclusively associated with CD45RBhigh cells and was not expressed during or after activation. The TSHr was not present on cells of the immune system during fetal or neonatal life. However, recombinant TSHβ was found to significantly enhance the phagocytic activity of dendritic cells from adult animals and to selectively augment IL-1β and IL-12 cytokine responses of dendritic cells following phagocytic activation. These findings identify a novel immune-endocrine bridge associated with professional APCs and naive T cells.

Section: Discussionmentioning

confidence: 99%

The Thyrotropin (Thyroid-Stimulating Hormone) Receptor Is Expressed on Murine Dendritic Cells and on a Subset of CD45RBhigh Lymph Node T Cells: Functional Role for Thyroid-Stimulating Hormone During Immune Activation

Bagriacik

Klein

2000

“…Mouse DC were prepared from bone marrow as previously described (39). Human monocytes were isolated with CD14 beads (Miltenyi Biotec, Auburn, CA) and differentiated into DC in RPMI 1640 with 10% FCS, IL-4 (50 ng/ml), and GM-CSF (1000 U/ml).…”

Section: Transduction Of DCmentioning

confidence: 99%

Intravenous Injection of a Lentiviral Vector Encoding NY-ESO-1 Induces an Effective CTL Response

Palmowski

Lopes

Ikeda

et al. 2004

101

121

Lentiviral vectors can efficiently transduce a variety of nondividing cells, including APCs. We assessed the immunogenicity of a lentiviral vector encoding the melanoma Ag NY-ESO-1 in HLA-A2 transgenic mice. Direct i.v. injection of NY-ESO-1 lentivirus induced NY-ESO-1157–165-specific CD8+ cells, detected ex vivo with an A2/H-2Kb chimeric class I tetramer. These NY-ESO-1157–165-specific CD8+ cells could be expanded by boosting with an NY-ESO-1 vaccinia virus and could kill NY-ESO-1157–165 peptide-pulsed targets in vivo. Such direct lentiviral vector injection was similar in potency to the injection of in vitro-transduced dendritic cells (DC). In addition, human monocyte-derived DC transduced by the NY-ESO-1 lentivirus stimulated an NY-ESO-1157–165-specific specific CTL clone. These data suggest that direct lentiviral transduction of DC in vivo might provide a powerful immunotherapeutic strategy.

“…DC were generated following the method of Inaba et al (22), with minor alterations. BM was harvested from the tibia and femur of C57BL/6 mice (n ϭ 4).…”

Section: Generation Of Murine Bone Marrow-derived DCmentioning

confidence: 99%

Oligosaccharides of Hyaluronan Are Potent Activators of Dendritic Cells

Termeer

Hennies

Voith

et al. 2000

347

242

The extracellular matrix component hyaluronan (HA) exists physiologically as a high m.w. polymer but is cleaved at sites of inflammation, where it will be contacted by dendritic cells (DC). To determine the effects of HA on DC, HA fragments of different size were established. Only small HA fragments of tetra- and hexasaccharide size (sHA), but not of intermediate size (m.w. 80,000–200,000) or high m.w. HA (m.w. 1,000,000–600,000) induced immunophenotypic maturation of human monocyte-derived DC (up-regulation of HLA-DR, B7-1/2, CD83, down-regulation of CD115). Likewise, only sHA increased DC production of the cytokines IL-1β, TNF-α, and IL-12 as well as their allostimulatory capacity. These effects were highly specific for sHA, because they were not induced by other glycosaminoglycans such as chondroitin sulfate or heparan sulfate or their fragmentation products. Interestingly, sHA-induced DC maturation does not involve the HA receptors CD44 or the receptor for hyaluronan-mediated motility, because DC from CD44-deficient mice and wild-type mice both responded similarly to sHA stimulation, whereas the receptor for hyaluronan-mediated motility is not detectable in DC. However, TNF-α is an essential mediator of sHA-induced DC maturation as shown by blocking studies with a soluble TNFR1. These findings suggest that during inflammation, interaction of DC with small HA fragments induce DC maturation.