Flt3-ligand and granulocyte colony-stimulating factor mobilize distinct human dendritic cell subsets in vivo.

Dendritic cells (DCs) have a unique ability to stimulate naive T cells. Recent evidence suggests that distinct DC subsets direct different classes of immune responses in vitro and in vivo. In humans, the monocyte-derived CD11c+ DCs induce T cells to produce Th1 cytokines in vitro, whereas the CD11c- plasmacytoid T cell-derived DCs elicit the production of Th2 cytokines.

Receptor revision of immunoglobulin heavy chain variable region genes in normal human B lymphocytes.

Contrary to the general precepts of the clonal selection theory, several recent studies have provided evidence for the secondary rearrangement of immunoglobulin (Ig) genes in peripheral lymphoid tissues. These analyses typically used transgenic mouse models and have only detected secondary recombination of Ig light chain genes. Although Ig heavy chain variable region (V(H)) genes encode a substantial element of antibody combining site specificity, there is scant evidence for V(H) gene rearrangement in the periphery, leaving the physiological importance of peripheral recombination questionable.

Immunobiology of dendritic cells.

Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response.

Naked antigen-presenting molecules on dendritic cells.

Antigen-presenting cells work to present peptides derived from exogenous and endogenous antigens to circulating T cells, sparking off an immune response. Dendritic cells are unique amongst antigen-presenting cells, not least for their newly described ability to circumvent the need to internalize exogenous antigens before presenting them.

Evidence and a novel hypothesis for the role of dendritic cells and Porphyromonas gingivalis in adult periodontitis.

We have proposed a novel overall hypothesis and approach to understanding the pathophysiology of adult periodontitis, one of the most common diseases that afflicts the US population. While mortality of the dentition is the most familiar outcome of adult periodontitis, its links with other more severe diseases, including coronary artery disease, respiratory diseases and pre-term labor, cannot be ignored. We have called attention to the many intriguing parallels between adult periodontitis and contact hypersensitivity (CHS).

Liver allotransplantation after extracorporeal hepatic support with transgenic (hCD55/hCD59) porcine livers: clinical results and lack of pig-to-human transmission of the porcine endogenous retrovirus.

Background: Whole organ extracorporeal perfusion of a genetically modified humanized (transgenic) pig liver has been proposed as a technology that may sustain patients with severe liver failure while awaiting human liver transplantation.

Methods: We report on two cases of successful extracorporeal perfusion of a transgenic pig liver in patients awaiting transplantation for fulminant hepatic failure. The pig livers used were transgenic for human CD55 (decay-accelerating factor) and human CD59.

CD40-CD40 ligand.

CD40 is a cell surface receptor that belongs to the tumor necrosis factor-R (TNF-R) family, and that was first identified and functionally characterized on B lymphocytes. Its critical role in T cell-dependent humoral immune responses was demonstrated by patients with the hyper-IgM syndrome, as well as by gene targeting in mice. However, in recent years it has become clear that CD40 is expressed much more broadly, including expression on monocytes, dendritic cells, endothelial cells, and epithelial cells.

T cells can induce somatic mutation in B cell receptor-engaged BL2 Burkitt's lymphoma cells independently of CD40-CD40 ligand interactions.

The B cell surface trigger(s) and the molecular mechanism(s) of somatic hypermutation remain unknown, partly because of the lack of amendable in vitro models. Recently, however, we reported that upon B cell receptor cross-linking and coculture with activated T cells, the Burkitt's lymphoma cell line BL2 introduces mutations in its IgVH gene in vitro. We now confirm the relevance of our culture model by establishing that the entire spectrum of somatic mutations observed in vivo, including insertions and deletions, could be found in the DNA of BL2 cells.

Molecular characterization of human IgG monoclonal antibodies specific for the major birch pollen allergen Bet v 1. Anti-allergen IgG can enhance the anaphylactic reaction.

We report the molecular characterization of five human monoclonal antibodies, BAB1-5 (BAB1: IgG(1); BAB4: IgG(2); BAB2, 3, 5: IgG(4)), with specificity for the major birch pollen allergen, Bet v 1. BAB1-5 were obtained after immunotherapy and contained a high degree of somatic mutations indicative of an antigen-driven affinity maturation process. While BAB1 inhibited the binding of patients IgE to Bet v 1, BAB2 increased IgE recognition of Bet v 1, and, even as Escherichia coli-expressed Fab, augmented Bet v 1-induced immediate type skin reactions.

In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas.

We have analyzed the presence of immature and mature dendritic cells (DCs) within adenocarcinoma of the breast using immunohistochemistry. Immature DCs were defined by expression of CD1a-, Langerin-, and intracellular major histocompatibility complex class II-rich vesicles. Mature DCs were defined by expression of CD83 and DC-Lamp.

The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surface.

We generated monoclonal antibody (mAb) DCGM4 by immunization with human dendritic cells (DC) from CD34+ progenitors cultured with granulocyte-macrophage colony-stimulating factor and TNF-alpha. mAb DCGM4 was selected for its reactivity with a cell surface epitope present only on a subset of DC. Reactivity was strongly enhanced by the Langerhans cell (LC) differentiation factor TGF-beta and down-regulated by CD40 ligation.

Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice.

Interleukin (IL) 17 is a proinflammatory cytokine secreted mainly by activated human memory CD4 T cells that induces IL-6, IL-8, and nitric oxide. Because IL-6 and IL-8 have been implicated in the pathogenesis of cervical cancer, we investigated the action of IL-17 on human cervical tumor cell lines in vitro and in vivo. We showed that in vitro, IL-17 increases IL-6 and IL-8 secretion by cervical carcinoma cell lines at both protein and mRNA levels.

Expression of a human IgG4 antibody, BAB2, with specificity for the major Birch pollen allergen, Bet v 1 in Escherichia coli: recombinant BAB2 Fabs enhance the allergic reaction.

Background: Antigen recognition by antibodies of different isotypes can result in completely different effects as exemplified by Type I allergy. While the IgE-antibody-mediated release of biological mediators constitutes the immunopathological basis for the immediate symptoms observed in allergic patients, allergen-specific IgG antibodies are thought to have protective effects.

Methods: Cell lines secreting five human monoclonal IgG antibodies (BAB1-BAB5) with specificity for the major birch pollen allergen Bet v 1 were established from a birch-pollen-allergic patient who had received birch- pollen-specific immunotherapy.

CD40 expression by human bronchial epithelial cells.

CD40 is a 50-kDa protein expressed on B cells, dendritic cells, monocytes and epithelial cells, but the distribution of CD40 expression in humans is not completely known. It binds to a ligand (CD40L) which is expressed essentially on activated T cells. The interaction between CD40 and CD40L plays important roles in immune responses.

Dendritic cells: a link between innate and adaptive immunity.

Dendritic cells (DC) constitute a unique system of cells able to induce primary immune responses. As a component of the innate immune system, DC organize and transfer information from the outside world to the cells of the adaptive immune system. DC can induce such contrasting states as active immune responsiveness or immunological tolerance.

Interleukin-4 and interleukin-13: their similarities and discrepancies.

Interleukin-4 (IL-4) and the closely related cytokine, interleukin-13 (IL-13) share many biological and immunoregulatory functions on B lymphocytes, monocytes, dendritic cells and fibroblasts. Both IL-4 and IL-13 genes are located in the same vicinity on chromosome 5 and display identical major regulatory sequences in their respective promoters, thus explaining their restricted secretion pattern to activated T cells and mast cells. The IL-4 and IL-13 receptors are multimeric and share at least one common chain called IL-4R alpha.

Dendritic cells enhance the differentiation of naïve B cells into plasma cells in vitro.

We have shown previously that in vitro-generated human dendritic cells have an effect on the response of B cells at various stages of their differentiation. In a culture system described for the in vitro induction of plasma-cell differentiation, it was reported that naïve B cells have a poor propensity to differentiate into plasma cells. In such a culture system, 12% of naïve B cells differentiated into plasma cells in the presence of IL-2 and IL-10, despite the interruption of CD40 signalling which is necessary for plasma-cell differentiation.

CD40L activation of dendritic cells down-regulates DORA, a novel member of the immunoglobulin superfamily.

Using a cDNA subtraction technique, a novel member of the immunoglobulin superfamily was isolated from human Dendritic cells (DC). This cDNA which we named DORA, for DOwn-Regulated by Activation encodes a protein belonging to the CD8 family of receptors containing a single V type loop domain with an associated J chain region, a transmembrane region containing an atypical tyrosine residue and a cytoplasmic domain containing three putative tyrosine phosphorylation sites. The hDORA gene has been localised to chromosome 16.

A novel lysosome-associated membrane glycoprotein, DC-LAMP, induced upon DC maturation, is transiently expressed in MHC class II compartment.

We have identified a novel lysosome-associated membrane glycoprotein localized on chromosome 3q26.3-q27, DC-LAMP, which is homologous to CD68. DC-LAMP mRNA is present only in lymphoid organs and DC.

Critical role of IL-12 in dendritic cell-induced differentiation of naive B lymphocytes.

Dendritic cells (DC) are potent APCs initiating immune responses. In a previous report, we demonstrated that DC directly enhance both proliferation and differentiation of CD40-activated naive and memory B cells. The present study deciphers the molecular mechanisms involved in DC-dependent regulation of B cell responses.

Antigen receptor engagement turns off the V(D)J recombination machinery in human tonsil B cells.

The germinal center (GC) is an anatomic compartment found in peripheral lymphoid organs, wherein B cells undergo clonal expansion, somatic mutation, switch recombination, and reactivate immunoglobulin gene V(D)J recombination. As a result of somatic mutation, some GC B cells develop higher affinity antibodies, whereas others suffer mutations that decrease affinity, and still others may become self-reactive. It has been proposed that secondary V(D)J rearrangements in GCs might rescue B cells whose receptors are damaged by somatic mutations.

Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection.

Local production of cytokines plays a critical role in the regulation of pathophysiologic processes leading to rejection of transplanted organs. In the present study, the possible role of interleukin-17 (IL-17), a recently identified cytokine with unique properties, was investigated. IL-17 is specifically produced by activated T cells, whereas biological activities are restricted to the activation of nonhematopoietic cells.