Galectin-1 is associated with hematopoietic cell engraftment in murine MHC-mismatched allotransplantation.

Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels.

A Phase I Trial of Atezolizumab and Varlilumab in Combination With Radiation in Patients With Metastatic NSCLC.

Introduction: Anti-programmed cell death 1 (PD-1) immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT).

Methods: We conducted an open-label, single-center, phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior programmed cell death ligand 1therapy.

Neutrophil Heterogeneity Is Modified during Acute Lung Inflammation in Apoa1-/- Mice.

Neutrophils play important roles in inflammatory airway diseases. In this study, we assessed whether apolipoprotein A-I modifies neutrophil heterogeneity as part of the mechanism by which it attenuates acute airway inflammation. Neutrophilic airway inflammation was induced by daily intranasal administration of LPS plus house dust mite (LPS+HDM) to Apoa1-/- and Apoa1+/+ mice for 3 d.

Functional implications of NHR-210 enrichment in C. elegans cephalic sheath glia: insights into metabolic and mitochondrial disruptions in Parkinson's disease models.

Glial cells constitute nearly half of the mammalian nervous system's cellular composition. The glia in C. elegans perform majority of tasks comparable to those conducted by their mammalian equivalents.

Low dose post-transplant cyclophosphamide and sirolimus induce mixed chimerism with CTLA4-Ig or lymphocyte depletion in an MHC-mismatched murine allotransplantation model.

Allogeneic hematopoietic cell transplantation (allo-HCT) offers a curative option for patients with certain non-malignant hematological diseases. High-dose post-transplant cyclophosphamide (PT-Cy) (200 mg/kg) and sirolimus (3 mg/kg), (HiC) synergistically induce stable mixed chimerism. Further, sirolimus and cytotoxic T lymphocyte-associated antigen-4 immunoglobulin (CTLA4-Ig), also known as Abatacept (Aba), promote immune tolerance and allograft survival.

Modulation of Neurotransmitter Pathways and Associated Metabolites by Systemic Silencing of Gut Genes in .

The gut is now recognized as the "second brain" of the human body due to its integral role in neuronal health and functioning. Although we know that the gut communicates with the brain via immunological factors, microbial metabolites, and neurotransmitters, the interplay of these systems remains poorly understood. To investigate this interplay, we silenced 48 genes that are exclusively or primarily expressed in the intestine.

Toll-like Receptor-9 (TLR-9) Signaling Is Crucial for Inducing Protective Immunity following Immunization with Genetically Modified Live Attenuated Parasites.

No human vaccine is available for visceral leishmaniasis (VL). Live attenuated centrin gene-deleted () parasite vaccine has been shown to induce robust innate immunity and provide protection in animal models. Toll-like receptors (TLRs) are expressed in innate immune cells and are essential for the early stages of infection.

Immunomodulatory effects of colchicine on peripheral blood mononuclear cell subpopulations in human obesity: Data from a randomized controlled trial.

Objective: Colchicine is known to reduce inflammation and improve endothelial cell function and atherosclerosis in obesity, but there is little knowledge of the specific circulating leukocyte populations that are modulated by colchicine.

Methods: A secondary analysis of a double-blind randomized controlled trial of colchicine 0.6 mg or placebo twice daily for 3 months on circulating leukocyte populations and regulation of the immune secretome in 35 adults with obesity was performed.

Comparative analysis of the immune response to RFA and cryoablation in a colon cancer mouse model.

The immune response to radiofrequency ablation (RFA) and cryoablation (CRA) was characterized and compared in a colon cancer mouse model. All studies were conducted under a research protocol approved by the National Institutes of Health, Clinical Center, Animal Care and Use Committee. BALB/cJ mice were inoculated with CT26 cells, and randomized to RFA, CRA, or sham treatment.

Stereodivergent Synthesis of ()-/()-β-Sulfonylacrylamides via Tandem Difunctionalization of Alkynes with Sulfinates and Isocyanides.

Stereoselective difunctionalizations of the terminal and internal alkynes with various sulfinates and isocyanides have been achieved to prepare ()-/()-β-sulfonylacrylamides. The ()-β-sulfonylacrylamides were generated via a one-pot process that involves the reaction of terminal alkynes with sulfinates and isocyanides in the presence of iodine in sequential manner. The ()-β-sulfonylacrylamides were prepared in a two-step synthesis via palladium(II)-catalyzed addition of isocyanide to ()-β-iodovinylsulfones synthesized from alkynes.

Identification of and resistant species in tobacco users and oral squamous cell carcinoma patients: Comparison of HiCrome agar and automated VITEK 2 system.

Introduction: Candida is most common fungal pathogen in the immunocompromised and medically ill patients. Higher prevalence of has been reported in tobacco users and oral squamous cell carcinoma (OSCC) patients which may be due to immunosuppression. Recently, emergence of (NAC) species resistant to conventional antifungal treatment has been observed that requires accurate identification of organisms at species level for reduction of progression of suspicious oral lesions toward malignancy.

Neutrophil-dendritic cell interaction plays an important role in live attenuated Leishmania vaccine induced immunity.

Background: Neutrophils are involved in the initial host responses to pathogens. Neutrophils can activate T cell responses either independently or through indirect involvement of Dendritic cells (DCs). Recently we have demonstrated direct neutrophil-T cell interactions that initiate adaptive immune responses following immunization with live attenuated Leishmania donovani centrin deleted parasite vaccine (LdCen-/-).

Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a widely available curative option for patients with sickle cell disease (SCD). Our original non-myeloablative haplo-HSCT trial employing post-transplant (PT) cyclophosphamide had a low incidence of GVHD but had high rejection rates. Here, we aimed to evaluate immune reconstitution following haplo-HSCT and identify cytokines and cells associated with graft rejection/engraftment.

Fasting-induced FOXO4 blunts human CD4 T helper cell responsiveness.

Intermittent fasting blunts inflammation in asthma and rheumatoid arthritis, suggesting that fasting may be exploited as an immune-modulatory intervention. However, the mechanisms underpinning the anti-inflammatory effects of fasting are poorly characterized. Here, we show that fasting in humans is sufficient to blunt CD4 T helper cell responsiveness.

Essential Role of Neutrophils in the Protective Immune Response Induced by a Live Attenuated Vaccine.

No licensed vaccine exists against visceral leishmaniasis (VL), a disease caused by the parasite. We have previously reported both macrophages and dendritic cells play important role in the protection induced by a live attenuated centrin gene-deleted ( ) parasite vaccine. The role of neutrophils in orchestrating the initial innate response to pathogens is widely recognized.

Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway.

Proliferation of dendritic cell (DC)-restricted progenitor cells in bone marrow compartment is tightly regulated at steady state and responds to multiple tissue-specific triggers during disturbed homeostasis such as obesity. DCs in the lung stem from a rapidly dividing DC-restricted progenitor cells and are effective at generating adaptive immune responses in allergic airway inflammation. Precisely, how DC-restricted progenitor expansion and differentiation are influenced by airway inflammation to maintain constant supply of myeloid DCs is poorly understood.

Immune cell phenotyping in low blood volumes for assessment of cardiovascular disease risk, development, and progression: a pilot study.

Background: Cardiovascular disease (CVD) is the leading cause of death in the world. Given the role of immune cells in atherosclerosis development and progression, effective methods for characterizing immune cell populations are needed, particularly among populations disproportionately at risk for CVD.

Results: By using a variety of antibodies combined in one staining protocol, we were able to identify granulocyte, lymphocyte, and monocyte sub-populations by CD-antigen expression from 500 µl of whole blood, enabling a more extensive comparison than what is possible with a complete blood count and differential (CBC).

Multiparametric Flow Cytometry Analysis of Naïve, Memory, and Effector T Cells.

Polychromatic flow cytometry enables the detection and characterization of markers which are helpful in defining phenotype of various cell subsets. Here we describe flow cytometry-based method to characterize phenotype of naïve, memory, and effector T cells. Being able to differentiate these cells is crucial in understanding immune response, and immune profiling.

Histone Deacetylase Inhibitor Modulates NKG2D Receptor Expression and Memory Phenotype of Human Gamma/Delta T Cells Upon Interaction With Tumor Cells.

The functional plasticity and anti-tumor potential of human γδ T cells have been widely studied. However, the epigenetic regulation of γδ T-cell/tumor cell interactions has been poorly investigated. In the present study, we show that treatment with the histone deacetylase inhibitor Valproic acid (VPA) significantly enhanced the expression and/or release of the NKG2D ligands MICA, MICB and ULBP-2, but not ULBP-1 in the pancreatic carcinoma cell line Panc89 and the prostate carcinoma cell line PC-3.

Ultrasensitive Quantification of Cytokine Proteins in Single Lymphocytes From Human Blood Following Stimulation.

In this study we demonstrate the feasibility of direct, quantitative measurement of cytokine proteins in single human CD8 lymphocytes from fresh peripheral blood of healthy donors following a brief stimulation. Cytokine-secreting cells were identified using cell surface "catch" reagents and single cell data were obtained by sorting of individual cytokine-secreting cells into 96 well plates containing lysis buffer followed by analysis using ultrasensitive immunoassays for interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). CD8 cells negative for cytokine production, as determined by the cell surface catch reagents were used as negative controls.

Low-density lipoprotein receptor-related protein 1 attenuates house dust mite-induced eosinophilic airway inflammation by suppressing dendritic cell-mediated adaptive immune responses.

Background: Low-density lipoprotein receptor-related protein 1 (LRP-1) is a scavenger receptor that regulates adaptive immunity and inflammation. LRP-1 is not known to modulate the pathogenesis of allergic asthma.

Objective: We sought to assess whether LRP-1 expression by dendritic cells (DCs) modulates adaptive immune responses in patients with house dust mite (HDM)-induced airways disease.

Expansion of FasL-Expressing CD5 B Cells in Type 1 Diabetes Patients.

Fas ligand drives insulitis in the non-obese diabetic mouse model of type 1 diabetes (T1D) and negatively regulates IL-10-producing (IL-10) CD5 B cells in pancreata. Relevance of these phenomena to the human disease is poorly understood. Here, using splenocytes from T1D, autoantibody (Ab), and non-diabetic (ND) human subjects, we show that a subpopulation of CD5 B cells that is characterized by expression of FasL (FasLCD5) was significantly elevated in T1D subjects, many of whom had significantly reduced frequency of IL-10CD5 B cells compared to Ab subjects.

Assessment of the Accuracy of Whole Blood/Serum Rapid Point-of-Care HIV Three Dot Test for Oral Fluid Specimens.

Background: Saliva rapid point of care HIV tests have proven advantages over blood-based HIV tests in terms of quality, rapidity and convenience.

Aim: To assess the sensitivity, specificity and reproducibility of saliva samples using the serum/ whole blood rapid test and to compare it with serum specimens.

Material & Methods: 52 seropositive and 52 seronegative patients were included in the study.