Phenotypic and Functional Diversities of Myeloid-Derived Suppressor Cells in Autoimmune Diseases.

Myeloid-derived suppressor cells (MDSCs) are identified as a heterogeneous population of cells with the function to suppress innate as well as adaptive immune responses. The initial studies of MDSCs were primarily focused on the field of animal tumor models or cancer patients. In cancer, MDSCs play the deleterious role to inhibit tumor immunity and to promote tumor development.

Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection.

The major metabolic feature of diabetes is hyperglycemia which has been linked to the diabetes inflammatory processes, and diabetes-related vulnerability to infection. In the present study, we assessed how glucose affected PBMCs in type I interferon (IFN) production and subsequent signaling. We found that the moderately elevated glucose promoted, and high glucose suppressed type I IFN production, respectively.

Immature Dendritic Cell Therapy Confers Durable Immune Modulation in an Antigen-Dependent and Antigen-Independent Manner in Nonobese Diabetic Mice.

Dendritic cell (DC) immunotherapy has been effective for prevention of type 1 diabetes (T1D) in NOD mice but fails to protect if initiated after active autoimmunity. As autoreactivity expands inter- and intramolecularly during disease progression, we investigated whether DCs unpulsed or pulsed with cell antigenic dominant determinants (DD), subdominant determinants (SD), and ignored determinants (ID) could prevent T1D in mice with advanced insulitis. We found that diabetes was significantly delayed by DC therapy.

A Novel Vaccine Targeting Glypican-3 as a Treatment for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate worldwide, with limited treatment options. Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored glycoprotein that is overexpressed in most HCC tissues but not in normal tissues. GPC3-targeting antibody therapy shows limited response in a clinical trial due to the lack of a tumor-specific cytotoxic T lymphocyte (CTL) response.

Type 1 Diabetes and Type 1 Interferonopathies: Localization of a Type 1 Common Thread of Virus Infection in the Pancreas.

Type 1 diabetes (T1D) has been associated with both genetic and environmental factors. Increasing incidence of T1D worldwide is prompting researchers to adopt different approaches to explain the biology of T1D, beyond the presence and activity of autoreactive lymphocytes. In this review, we propose inflammatory pathways as triggers for T1D.

PD-1/PD-L1 Interaction Maintains Allogeneic Immune Tolerance Induced by Administration of Ultraviolet B-Irradiated Immature Dendritic Cells.

Our previous study demonstrated that transfusion of ultraviolet B-irradiated immature dendritic cells (UVB-iDCs) induced alloantigen-specific tolerance between two different strains of mice. Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been suggested to play an important role in maintaining immune tolerance. In the present study, we seek to address whether PD-1/PD-L1 plays a role in the maintenance of UVB-iDC-induced tolerance.

Potent antigen-specific immune response induced by infusion of spleen cells coupled with succinimidyl-4-(N-maleimidomethyl cyclohexane)-1-carboxylate (SMCC) conjugated antigens.

In the present study, we report our recently developed new approach to inducing antigen-specific immune response. We use two nucleophilic substitution "click" chemistry processes to successfully couple protein antigens or peptides to mouse spleen cells or T cells by a heterobifunctional crosslinker, succinimidyl-4-(N-maleimidomethyl cyclohexane)-1-carboxylate (SMCC) or sulfo-SMCC. SMCC and its water-soluble analog sulfo-SMCC contain N-hydroxysuccinimide (NHS) ester and maleimide groups, which allow stable covalent conjugation of amine- and sulfhydryl-containing molecules in trans.

Immunosuppressive CD11b+Ly6Chi monocytes in pristane-induced lupus mouse model.

Myeloid-derived suppressor cells with immunosuppressive functions have been described to be associated with one of the mechanisms by which malignant tumors escape immune surveillance. However, little is known about the role of myeloid-derived suppressor cells in autoimmunity. In the current study, when we attempted to characterize the peritoneal cells in pristane-induced lupus model, as reported previously, we observed that there were markedly increased CD11b(+)Ly6C(hi) monocytes.

Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP100(25-33) peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma.

It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP10025-33 peptide-coupled syngeneic spleen cells in a mouse model of melanoma.

Effects of type 1 diabetes-associated IFIH1 polymorphisms on MDA5 function and expression.

Recent evidence has highlighted the role of the innate immune system in type 1 diabetes (T1D) pathogenesis. Specifically, aberrant activation of the interferon response prior to seroconversion of T1D-associated autoantibodies supports a role for the interferon response as a precipitating event toward activation of autoimmunity. Melanoma differentiation-associated protein 5 (MDA5), encoded by IFIH1, mediates the innate immune system's interferon response to certain viral species that form double-stranded RNA (dsRNA), the MDA5 ligand, during their life cycle.

Infusion of Sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate-Conjugated MOG35-55-Coupled Spleen Cells Effectively Prevents and Reverses Experimental Autoimmune Encephalomyelitis in Mice.

In this study, we have evaluated our recently developed method for antigen-cell coupling using sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate (sulfo-SMCC) heterobifunctional crosslinker in prevention and reversal of experimental autoimmune encephalomyelitis (EAE). We demonstrate that infusion of MOG35-55-coupled spleen cells (MOG-SP) significantly prevents and reverses EAE. Further studies show that the protected animals exhibit significantly delayed EAE upon EAE reinduction.

Thioredoxin priming prolongs lung allograft survival by promoting immune tolerance.

Tolerance to allograft antigen is the major challenge and final goal of transplant medicine. Our previous study demonstrated that thioredoxin-1 (Trx) priming of donor lung significantly protected allogeneic lung graft. To determine whether Trx priming of donor lung inhibits allograft rejection, extends allograft survival and induces immune tolerance, orthotopic left lung transplantation was performed from Lewis to Sprague-Dawley rats without immunosuppression.

A combination dual-sized microparticle system modulates dendritic cells and prevents type 1 diabetes in prediabetic NOD mice.

We developed a novel poly(lactic-co-glycolic acid)-based, microparticle (MP) system providing concurrent delivery of multiple encapsulated immuno-suppressive factors and antigen, for in vivo conditioning of dendritic cells (DCs) toward a tolerance promoting pathway. Subcutaneous administration prevents onset of type 1 diabetes (T1D) in NOD mice. Two MP sizes were made: phagocytosable MPs were fabricated encapsulating vitamin D3 or insulin B(9-23) peptide, while unphagocytosable MPs were fabricated encapsulating TGF-β1 or GM-CSF.

[Evaluation of neutrophilic CD64 index as a diagnostic marker of bacterial infection in blood diseases].

This study was aimed to investigate the value of neutrophilic CD64 index (nCD64 index) as a diagnostic marker of bacterial infection in hematologic diseases. Experimental data of 232 patients with hematologic diseases were analyzed retrospectively. The nCD64 index was detected by flow cytometry and was compared with the levels of erythrocyte sedimentation rate (ESR), C reaction protein (CRP) and fibrinogen respectively.

Increased IFN-α-producing plasmacytoid dendritic cells (pDCs) in human Th1-mediated type 1 diabetes: pDCs augment Th1 responses through IFN-α production.

Increasing evidence suggests that type 1 IFN (IFN-αβ) is associated with pathogenesis of Th1-mediated type 1 diabetes (T1D). A major source of IFN-αβ is plasmacytoid dendritic cells (pDCs). In this study, we analyzed peripheral blood pDC numbers and functions in at-risk, new-onset, and established T1D patients and controls.

C-Abl inhibitor imatinib enhances insulin production by β cells: c-Abl negatively regulates insulin production via interfering with the expression of NKx2.2 and GLUT-2.

Chronic myelogenous leukemia patients treated with tyrosine kinase inhibitor, Imatinib, were shown to have increased serum levels of C-peptide. Imatinib specifically inhibits the tyrosine kinase, c-Abl. However, the mechanism of how Imatinib treatment can lead to increased insulin level is unclear.

Anti-CD3 antibody treatment induces hypoglycemia and super tolerance to glucose challenge in mice through enhancing glucose consumption by activated lymphocytes.

Anti-CD3 antibody has been employed for various immune-mediated disorders. However, whether anti-CD3 administration leads to rapid metabolic alternation has not been well investigated. In the current study, we studied how anti-CD3 treatment affected blood glucose levels in mice.

Characterization of Bone Marrow-Derived Dendritic Cells Developed in Serum-Free Media and their Ability to Prevent Type 1 Diabetes in Nonobese Diabetic Mice.

Dendritic cells (DC) have been investigated as a cell-based therapy for Type 1 Diabetes (T1D). BM-DC expanded with GM-CSF and IL-4 is typically cultured with fetal bovine serum (FBS). The effect of FBS on NOD BM-DC has not been extensively studied.

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice.

Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice.

Ex vivo expansion of regulatory T cells for clinical applications against graft-versus-host disease in allogeneic hematopoietic stem cell transplantation.

Objective: To review the characteristics of regulatory T cells (Tregs) and ex vivo expansion of Tregs for treatment of graft-versus-host disease (GVHD).

Data Sources: The data used in this review were retrieved from PubMed (1970-2013). The terms "ex vivo expansion", "regulatory T cell", and "graft-versus-host disease" were used for literature search.

Anti-thymocyte globulin (ATG) differentially depletes naïve and memory T cells and permits memory-type regulatory T cells in nonobese diabetic mice.

Background: ATG has been employed to deplete T cells in several immune-mediated conditions. However, whether ATG administration affects naïve and memory T cell differently is largely unknown. THE CONTEXT AND PURPOSE OF THE STUDY: In this study, we assessed how murine ATG therapy affected T cell subsets in NOD mice, based on their regulatory and naïve or memory phenotype, as well as its influence on antigen-specific immune responses.

The tyrphostin agent AG490 prevents and reverses type 1 diabetes in NOD mice.

Background: Recent studies in the NOD (non-obese diabetic) mouse model of type 1 diabetes (T1D) support the notion that tyrosine kinase inhibitors have the potential for modulating disease development. However, the therapeutic effects of AG490 on the development of T1D are unknown.

Materials And Methods: Female NOD mice were treated with AG490 (i.

Incipient Coombs' test negative autoimmune hemolytic anemia precedes non-Hodgkin's lymphoma.

The cases of lymphoma accompanied or preceded by Coombs' test positive autoimmune hemolytic anemia (AIHA) have been reported. However, Coombs' test negative AIHA prior to the diagnosis of lymphoma was rarely described. Herein, this article reports a case of non-Hodgkin's lymphoma (NHL) preceded about 1.