Induction of potent CD8 T cell cytotoxicity by specific targeting of antigen to cross-presenting dendritic cells in vivo via murine or human XCR1.

Current subunit vaccines are incapable of inducing Ag-specific CD8(+) T cell cytotoxicity needed for the defense of certain infections and for therapy of neoplastic diseases. In experimental vaccines, cytotoxic responses can be elicited by targeting of Ag into cross-presenting dendritic cells (DC), but almost all available systems use target molecules also expressed on other cells and thus lack the desired specificity. In the present work, we induced CD8(+) T cell cytotoxicity by targeting of Ag to XCR1, a chemokine receptor exclusively expressed on murine and human cross-presenting DC.

Ontogenic, Phenotypic, and Functional Characterization of XCR1(+) Dendritic Cells Leads to a Consistent Classification of Intestinal Dendritic Cells Based on the Expression of XCR1 and SIRPα.

In the past, lack of lineage markers confounded the classification of dendritic cells (DC) in the intestine and impeded a full understanding of their location and function. We have recently shown that the chemokine receptor XCR1 is a lineage marker for cross-presenting DC in the spleen. Now, we provide evidence that intestinal XCR1(+) DC largely, but not fully, overlap with CD103(+) CD11b(-) DC, the hypothesized correlate of "cross-presenting DC" in the intestine, and are selectively dependent in their development on the transcription factor Batf3.

[Echoendoscopy in digestive subepithelial lesions: review of the literature].

Injury or bulging subepithelial mucosal lesions are covered with normal mucosa, usually asymptomatic. Most are diagnosed in radiology or endoscopy, which may correspond to any layer of the body wall (intramural) or non-belonging to the wall (extramural). This article describes studies for analysis of endoscopic ultrasonography (EUS) as a diagnostic method with high accuracy on the finding of subepithelial lesion.

Expression of XCR1 Characterizes the Batf3-Dependent Lineage of Dendritic Cells Capable of Antigen Cross-Presentation.

Cross-presentation of antigen by dendritic cells (DCs) to CD8(+) T cells is a fundamentally important mechanism in the defense against pathogens and tumors. Due to the lack of an appropriate lineage marker, cross-presenting DCs in the mouse are provisionally classified as "Batf3-IRF-8-Id2-dependent DCs" or as "CD8(+) DCs" in the spleen, and as "CD103(+)CD11b(-) DCs" in the periphery. We have now generated a mAb to XCR1, a chemokine receptor which is specifically expressed on CD8(+) DCs and a subpopulation of double negative DCs in the spleen.

The Role of XCR1 and its Ligand XCL1 in Antigen Cross-Presentation by Murine and Human Dendritic Cells.

Recently, the chemokine receptor XCR1 has been found to be exclusively expressed on a subset of dendritic cell (DC) known to be involved in antigen cross-presentation. This review aims to summarize the known biology of the XCR1 receptor and its chemokine ligand XCL1, both in the mouse and the human. Further, any involvement of this receptor-ligand pair in antigen uptake, cross-presentation, and induction of innate and adaptive cytotoxic immunity is explored.

The MagA protein of Magnetospirilla is not involved in bacterial magnetite biomineralization.

Magnetotactic bacteria have the ability to orient along geomagnetic field lines based on the formation of magnetosomes, which are intracellular nanometer-sized, membrane-enclosed magnetic iron minerals. The formation of these unique bacterial organelles involves several processes, such as cytoplasmic membrane invagination and magnetosome vesicle formation, the accumulation of iron in the vesicles, and the crystallization of magnetite. Previous studies suggested that the magA gene encodes a magnetosome-directed ferrous iron transporter with a supposedly essential function for magnetosome formation in Magnetospirillum magneticum AMB-1 that may cause magnetite biomineralization if expressed in mammalian cells.

The cation diffusion facilitator proteins MamB and MamM of Magnetospirillum gryphiswaldense have distinct and complex functions, and are involved in magnetite biomineralization and magnetosome membrane assembly.

Magnetotactic bacteria form chains of intracellular membrane-enclosed, nanometre-sized magnetite crystals for navigation along the earth's magnetic field. The assembly of these prokaryotic organelles requires several specific polypeptides. Among the most abundant proteins associated with the magnetosome membrane of Magnetospirillum gryphiswaldense are MamB and MamM, which were implicated in magnetosomal iron transport because of their similarity to the cation diffusion facilitator family.

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

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.

An avoidable death in police custody?

An obviously inebriated 36-year-old man was found in a helpless condition on a pavement. When he was brought to a police station, a doctor certified the individual to be fit to be held in custody. He was unresponsive when the officers tried to wake him the next morning but was allowed to sleep on until he was found dead in his cell at mid day.

Selective expression of the chemokine receptor XCR1 on cross-presenting dendritic cells determines cooperation with CD8+ T cells.

The expression of the chemokine receptor XCR1 and the function of its ligand XCL1 (otherwise referred to as ATAC, lymphotactin, or SCM-1) remained elusive to date. In the present report we demonstrated that XCR1 is exclusively expressed on murine CD8(+) dendritic cells (DCs) and showed that XCL1 is a potent and highly specific chemoattractant for this DC subset. CD8(+) T cells abundantly secreted XCL1 8-36 hr after antigen recognition on CD8(+) DCs in vivo, in a period in which stable T cell-DC interactions are known to occur.

Compartmentalization of cAMP-dependent signaling by phosphodiesterase-4D is involved in the regulation of vasopressin-mediated water reabsorption in renal principal cells.

The cAMP/protein kinase A (PKA)-dependent insertion of water channel aquaporin-2 (AQP2)-bearing vesicles into the plasma membrane in renal collecting duct principal cells (AQP2 shuttle) constitutes the molecular basis of arginine vasopressin (AVP)-regulated water reabsorption. cAMP/PKA signaling systems are compartmentalized by A kinase anchoring proteins (AKAP) that tether PKA to subcellular sites and by phosphodiesterases (PDE) that terminate PKA signaling through hydrolysis of localized cAMP. In primary cultured principal cells, AVP causes focal activation of PKA.

Spatial organisation of AKAP18 and PDE4 isoforms in renal collecting duct principal cells.

A plethora of stimuli including hormones and neurotransmitters mediate a rise of the cellular level of cAMP and thereby activation of protein kinase A (PKA). PKA phosphorylates and thereby modulates the activity of a wide range of cellular targets. It is now appreciated that different stimuli induce the activation of PKA at specific sites where the kinase phosphorylates particular substrates in close proximity.

Compartmentalized cAMP signalling regulates vasopressin-mediated water reabsorption by controlling aquaporin-2.

The cAMP/PKA (protein kinase A) signalling pathway is activated by a plethora of stimuli. To facilitate the specificity of a cellular response, signal transduction complexes are formed and segregated to discrete sites (compartmentalization). cAMP/PKA signalling compartments are maintained by AKAPs (A-kinase anchoring proteins) which bind PKA and other signalling proteins, and by PDEs (phosphodiesterases).

Diagnosis and presentation of fatal myocarditis.

The clinical presentation of myocarditis is highly variable, and histopathology is thus considered to be the cornerstone of diagnosis. We studied how accurately myocarditis was diagnosed in a series of routine autopsies and how fatal myocarditis presents clinically. All death certificates with myocarditis recorded as the underlying cause of death in Finland in 1970 to 1998 were collected retrospectively (N = 639).

Apoptotic cardiomyocyte death in fatal myocarditis.

Acute myocarditis is often a self-limited process with a good outcome. Experimental animal studies have found that cardiomyocyte apoptosis occurs in severe forms of myocarditis. We studied whether cardiomyocyte apoptosis plays a role in the development of fatal acute human myocarditis.

Identification of a novel A-kinase anchoring protein 18 isoform and evidence for its role in the vasopressin-induced aquaporin-2 shuttle in renal principal cells.

Arginine vasopressin (AVP) increases the water permeability of renal collecting duct principal cells by inducing the fusion of vesicles containing the water channel aquaporin-2 (AQP2) with the plasma membrane (AQP2 shuttle). This event is initiated by activation of vasopressin V2 receptors, followed by an elevation of cAMP and the activation of protein kinase A (PKA). The tethering of PKA to subcellular compartments by protein kinase A anchoring proteins (AKAPs) is a prerequisite for the AQP2 shuttle.

CD40 ligand is selectively expressed on CD4+ T cells and platelets: implications for CD40-CD40L signalling in atherosclerosis.

Atherosclerosis is a degenerative inflammatory disease of the vascular system. Endothelial cells (ECs), smooth muscle cells, and macrophages, key elements in atherosclerosis, all have the potential to express the CD40 receptor and are thus susceptible to potent pro-inflammatory signals by CD40 ligand (CD40L)-bearing cells. CD40L is a TNF-alpha-related membrane protein originally identified on activated T cells.

Three-dimensional vestibular eye and head reflexes of the chameleon: characteristics of gain and phase and effects of eye position on orientation of ocular rotation axes during stimulation in yaw direction.

We investigated gaze-stabilizing reflexes in the chameleon using the three-dimensional search-coil technique. Animals were rotated sinusoidally around an earth-vertical axis under head-fixed and head-free conditions, in the dark and in the light. Gain, phase and the influence of eye position on vestibulo-ocular reflex rotation axes were studied.

ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells.

Endothelial cells (EC) play a central role in inflammatory immune responses and efficiently induce effector functions in T cells, despite lacking the classical costimulatory ligands CD80 and CD86. By using the mAb HIL-131 we now demonstrate that human inducible costimulator-ligand (ICOS-L), a molecule related to CD80/CD86, is constitutively expressed on human EC in vivo. In vitro, ICOS-L expression was strongly enhanced on human umbilical vein EC and microvascular EC by the inflammatory cytokines tumor necrosis factor alpha and IL-1beta, and to a lower extent by stimulation of EC by CD40 or lipopolysaccharide.

Ht31: the first protein kinase A anchoring protein to integrate protein kinase A and Rho signaling.

In an attempt to isolate protein kinase A anchoring proteins (AKAPs) involved in vasopressin-mediated water reabsorbtion, the complete sequence of the human AKAP Ht31 was determined and a partial cDNA of its rat orthologue (Rt31) was cloned. The Ht31 cDNA includes the estrogen receptor cofactor Brx and the RhoA GDP/GTP exchange factor proto-lymphoid blast crisis (Lbc) sequences. The Ht31 gene was assigned to chromosome 15 (region q24-q25).

Ocular counterroll modulates the preferred direction of saccade-related pontine burst neurons in the monkey.

Saccade-related burst neurons in the paramedian pontine reticular formation (PPRF) of the head-restrained monkey provide a phasic velocity signal to extraocular motoneurons for the generation of rapid eye movements. In the superior colliculus (SC), which directly projects to the PPRF, the motor command for conjugate saccades with the head restrained in a roll position is represented in a reference frame in between oculocentric and space-fixed coordinates with a clear bias toward gravity. Here we studied the preferred direction of premotor burst neurons in the PPRF during static head roll to characterize their frame of reference with respect to head and eye position.

The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40.

Recently, we have demonstrated that human platelets carry preformed CD40 ligand (CD154) molecules, which rapidly appear on the platelet surface following stimulation by thrombin. Once on the surface, platelet CD154 induces an inflammatory reaction of CD40-bearing endothelial cells. This study shows that strong platelet agonists other than thrombin also lead to the expression of CD154 on the platelet surface.

Chameleon eye position obeys Listing's law.

Listing's law (LL) states that 3D-eye positions lie in a plane, when they are described as single-axis rotations from the primary position. This implies that the degrees of freedom of eye movements are reduced from three to two. Various hypotheses exist, regarding the implementation of LL.