Antigen-Induced but Not Innate Memory CD8 T Cells Express NKG2D and Are Recruited to the Lung Parenchyma upon Viral Infection.

The pool of memory-phenotype CD8 T cells is composed of Ag-induced (AI) and cytokine-induced innate (IN) cells. IN cells have been described as having properties similar to those of AI memory cells. However, we found that pathogen-induced AI memory cells can be distinguished in mice from naturally generated IN memory cells by surface expression of NKG2D.

Immune signatures of protective spleen memory CD8 T cells.

Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge.

Depth-resolved registration of transesophageal echo to x-ray fluoroscopy using an inverse geometry fluoroscopy system.

Purpose: Image registration between standard x-ray fluoroscopy and transesophageal echocardiography (TEE) has recently been proposed. Scanning-beam digital x-ray (SBDX) is an inverse geometry fluoroscopy system designed for cardiac procedures. This study presents a method for 3D registration of SBDX and TEE images based on the tomosynthesis and 3D tracking capabilities of SBDX.

Intravenous Followed by X-ray Fused with MRI-Guided Transendocardial Mesenchymal Stem Cell Injection Improves Contractility Reserve in a Swine Model of Myocardial Infarction.

The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed.

Feasibility of CT-based 3D anatomic mapping with a scanning-beam digital x-ray (SBDX) system.

This study investigates the feasibility of obtaining CT-derived 3D surfaces from data provided by the scanning-beam digital x-ray (SBDX) system. Simulated SBDX short-scan acquisitions of a Shepp-Logan and a thorax phantom containing a high contrast spherical volume were generated. 3D reconstructions were performed using a penalized weighted least squares method with total variation regularization (PWLS-TV), as well as a more efficient variant employing gridding of projection data to parallel rays (gPWLS-TV).

Detector, collimator and real-time reconstructor for a new scanning-beam digital x-ray (SBDX) prototype.

Scanning-beam digital x-ray (SBDX) is an inverse geometry fluoroscopy system for low dose cardiac imaging. The use of a narrow scanned x-ray beam in SBDX reduces detected x-ray scatter and improves dose efficiency, however the tight beam collimation also limits the maximum achievable x-ray fluence. To increase the fluence available for imaging, we have constructed a new SBDX prototype with a wider x-ray beam, larger-area detector, and new real-time image reconstructor.

Monte Carlo simulation of inverse geometry x-ray fluoroscopy using a modified MC-GPU framework.

Scanning-Beam Digital X-ray (SBDX) is a technology for low-dose fluoroscopy that employs inverse geometry x-ray beam scanning. To assist with rapid modeling of inverse geometry x-ray systems, we have developed a Monte Carlo (MC) simulation tool based on the MC-GPU framework. MC-GPU version 1.

Overexpression of the transcription factor Sp1 activates the OAS-RNAse L-RIG-I pathway.

Deregulated expression of oncogenes or transcription factors such as specificity protein 1 (Sp1) is observed in many human cancers and plays a role in tumor maintenance. Paradoxically in untransformed cells, Sp1 overexpression induces late apoptosis but the early intrinsic response is poorly characterized. In the present work, we studied increased Sp1 level consequences in untransformed cells and showed that it turns on an early innate immune transcriptome.

Calibration-free coronary artery measurements for interventional device sizing using inverse geometry x-ray fluoroscopy: validation.

Proper sizing of interventional devices to match coronary vessel dimensions improves procedural efficiency and therapeutic outcomes. We have developed a method that uses an inverse geometry x-ray fluoroscopy system [scanning beam digital x-ray (SBDX)] to automatically determine vessel dimensions from angiograms without the need for magnification calibration or optimal views. For each frame period (1/15th of a second), SBDX acquires a sequence of narrow beam projections and performs digital tomosynthesis at multiple plane positions.

Calibration-Free Coronary Artery Measurements for Interventional Device Sizing using Inverse Geometry X-ray Fluoroscopy: Validation.

Proper sizing of interventional devices to match coronary vessel dimensions improves procedural efficiency and therapeutic outcomes. We have developed a novel method using inverse geometry x-ray fluoroscopy to automatically determine vessel dimensions without the need for magnification calibration or optimal views. To validate this method , we compared results to intravascular ultrasound (IVUS) and coronary computed tomography angiography (CCTA) in a healthy porcine model.

Monoplane Stereoscopic Imaging Method for Inverse Geometry X-ray Fluoroscopy.

Scanning Beam Digital X-ray (SBDX) is a low-dose inverse geometry fluoroscopic system for cardiac interventional procedures. The system performs x-ray tomosynthesis at multiple planes in each frame period and combines the tomosynthetic images into a projection-like composite image for fluoroscopic display. We present a novel method of stereoscopic imaging using SBDX, in which two slightly offset projection-like images are reconstructed from the same scan data by utilizing raw data from two different detector regions.

Generation of transgenic mice expressing EGFP protein fused to NP68 MHC class I epitope using lentivirus vectors.

Immune tolerance to self-antigens is a complex process that utilizes multiple mechanisms working in concert to maintain homeostasis and prevent autoimmunity. Considerable progress in deciphering the mechanisms controlling the activation or deletion of T cells has been made by using T cell receptor (TCR) transgenic mice. One such model is the F5 model in which CD8 T cells express a TCR specific for an epitope derived from the influenza NP68 protein.

Multimodality image fusion to guide peripheral artery chronic total arterial occlusion recanalization in a swine carotid artery occlusion model: unblinding the interventionalist.

Objectives: To demonstrate the feasibility of magnetic resonance imaging (MRI) to X-ray fluoroscopy (XRF) image fusion to guide peripheral artery chronic total occlusion (CTO) recanalization.

Background: Endovascular peripheral artery CTO revascularization is minimally invasive, but challenging, because the occlusion is poorly visualized under XRF. Devices may steer out of the artery, which can lead to severe perforation.

NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells.

Pattern recognition receptors (PRR), like Toll-like receptors (TLR) and NOD-like receptors (NLR), are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells.

T inflammatory memory CD8 T cells participate to antiviral response and generate secondary memory cells with an advantage in XCL1 production.

Besides the classically described subsets of memory CD8 T cells generated under infectious conditions, are T inflammatory memory cells generated under sterile priming conditions, such as sensitization to allergens. Although not fully differentiated as pathogen-induced memory cells, they display memory properties that distinguish them from naive CD8 T cells. Given these memory cells are generated in an antigen-specific context that is devoid of pathogen-derived danger signals and CD4 T cell help, we herein questioned whether they maintained their activation and differentiation potential, could be recruited in an immune response directed against a pathogen expressing their cognate antigen and further differentiate in fully competent secondary memory cells.

Targeted transendocardial therapeutic delivery guided by MRI-x-ray image fusion.

Objectives: To validate a multi-modality image fusion approach to guide catheter-based, targeted transendocardial therapeutic delivery in a swine myocardial infarction (MI) model.

Background: Biologic agents such as stem cells may curb post MI adverse ventricular remodeling if delivered by a transendocardial catheter directly into the infarct border. 3D visualization of the infarct and other cardiac surfaces is required to perform this task.

Calibration-free device sizing using an inverse geometry x-ray system.

Purpose: Quantitative coronary angiography (QCA) can be used to support device size selection for cardiovascular interventions. The accuracy of QCA measurements using conventional x-ray fluoroscopy depends on proper calibration using a reference object and avoiding vessel foreshortening. The authors have developed a novel interventional device sizing method using the inverse geometry scanning-beam digital x-ray (SBDX) fluoroscopy system.

Three-dimensional tracking of cardiac catheters using an inverse geometry x-ray fluoroscopy system.

Purpose: Scanning beam digital x-ray (SBDX) is an inverse geometry fluoroscopic system with high dose efficiency and the ability to perform continuous real-time tomosynthesis at multiple planes. This study describes a tomosynthesis-based method for 3D tracking of high-contrast objects and present the first experimental investigation of cardiac catheter tracking using a prototype SBDX system.

Methods: The 3D tracking algorithm utilizes the stack of regularly spaced tomosynthetic planes that are generated by SBDX after each frame period (15 frames/s).

CpG promotes cross-presentation of dead cell-associated antigens by pre-CD8α+ dendritic cells [corrected].

Cross-presentation of cell-associated Ags by dendritic cells (DC) plays an important role in immunity. DC in lymphoid tissues are short lived, being continuously replaced by precursors that proliferate and differentiate locally. Paradoxically, although TLR ligands promote immune responses and stimulate DC replenishment, they impair the cross-priming capacity of terminally differentiated splenic CD8α(+) DC, the major subset involved in cross-priming.

Maintenance of CCL5 mRNA stores by post-effector and memory CD8 T cells is dependent on transcription and is coupled to increased mRNA stability.

Immunological memory is associated with the display of improved effector functions by cells of the adaptive immune system. The storage of untranslated mRNA coding for the CCL5 chemokine by CD8 memory cells is a new process supporting the immediate display of an effector function. Here, we show that, after induction during the primary response, high CCL5 mRNA levels are specifically preserved in CD8 T cells.

Cell-autonomous CCL5 transcription by memory CD8 T cells is regulated by IL-4.

Immunological memory is associated with the display of improved effector functions. The maintenance by CD8 memory cells of high levels of untranslated CCL5 mRNA allows these cells to immediately secrete this chemokine upon Ag stimulation. Untranslated mRNA storage is a newly described process supporting the immediate display of an effector function by memory lymphocytes.

TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation.

TLR have a crucial role in the detection of microbial infection in mammals. Until recently, most investigations on TLR have focused on cells of the innate immune system and on the role of TLR in the initiation of antigen-specific responses following recognition of microbial products by APC. Here, we report that murine T cells express TLR1, TLR2, TLR6, TLR7 and TLR9 mRNA.

Flt3 ligand-generated murine plasmacytoid and conventional dendritic cells differ in their capacity to prime naive CD8 T cells and to generate memory cells in vivo.

Mature dendritic cells (DCs) have the capacity to induce efficient primary T cell response and effector cell differentiation. Thus, these cells are a major tool in the design of various immunotherapeutic protocols. We have tested the capacity of different subsets of matured DCs pulsed with a peptide to induce the differentiation of naive CD8 T cells into memory cells in vivo.

Restriction of de novo nucleotide biosynthesis interferes with clonal expansion and differentiation into effector and memory CD8 T cells.

Nucleotide synthesis inhibitors are currently used in neoplastic diseases or as immunosuppressive agents for the prevention of acute rejection in organ transplantation and the treatment of autoimmune disorders. We have previously described that these inhibitors interfere with proliferation and survival of primary T cells in vitro. However, the precise effects of nucleotide restriction on effector and memory functions have not been elucidated.