Результаты поиска

Recovery of pancreatic beta cells in response to long-term normoglycemia after pancreas or islet transplantation in severely streptozotocin diabetic adult rats.

In the well-established, high-dose streptozotocin diabetic rat model, it is unknown whether normoglycemia after pancreas or islet transplantation may induce the expression of the glucose recognition structures and stimulate the replication of the few surviving pancreatic beta cells. Therefore, the endocrine pancreatic tissue was examined immunocytochemically in streptozotocin-treated major histocompatibility complex congenic Lewis rats at 10 and 100 days after transplantation of whole pancreata or isolated islets implanted under the kidney capsule. In the diabetic state the pancreatic beta cel…

Immunogenetics of inflammatory myopathies.

The genes most commonly considered when investigating immunogenetic associations with autoimmune diseases, including inflammatory muscle disease (IMD), are those encoded in the major histocompatibility complex (MHC), the T-cell receptor (TCR) genes and the immunoglobulin genes. In caucasoids HLA DR3 is associated with adult polymyositis (PM) and juvenile dermatomyositis (JDM) and is probably increased in frequency in adult DM. In inclusion body myositis (IBM) DR3 and DR1 have been separately reported to be increased but few patients have been analysed. The DR3 in IMD is almost always present o…

An Open-Label Study of the Safety and Efficacy of Tag-7 Gene-Modified Tumor Cells-Based Vaccine in Patients with Locally Advanced or Metastatic Malignant Melanoma or Renal Cell Cancer.

LESSONS LEARNED: This study showed that carefully selected patients with locally advanced and metastatic forms of malignant melanoma and ren … asis of ISF production (Fig. 1). The median OS was 6.6 years in the favorable prognosis (FP) group (major histocompatibility complex class I polypeptide-related sequence A [MICA] level ≤582 pg/mL, n = 15) and 4.6 months in the unfavorable (UF) group (MICA level >582 pg/mL, n = 12; p < .0001). No significant differences were found between classification trees based on ISFs (transf …

A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines.

Besides the isolation and identification of major histocompatibility complex I-restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective antitumor CD8+ T-cell-mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid pipeline for the downstream selection of clinically relevant peptides and the subsequent creation of therapeutic cancer vaccines are of utmost importance. Indeed, the use of peptides for eliciting specific antitumor adaptive immunity is hindered by two main limitations: the efficient selection of th…

Proteome-wide analysis of Coxiella burnetii for conserved T-cell epitopes with presentation across multiple host species.

BACKGROUND: Coxiella burnetii is the Gram-negative bacterium responsible for Q fever in humans and coxiellosis in domesticated agricultural … The purpose of this study was to identify C. burnetii proteins bearing epitopes that interact with major histocompatibility complexes (MHC) from multiple host species (human, mouse, and cattle). RESULTS: Of the annotated 1815 proteins from the Nine Mile Phase I (RSA 493) assembly, 402 proteins were removed from analysis due to a lack of inter-isolate conservation. An additional …

Sepsis-induced changes in macrophage co-stimulatory molecule expression: CD86 as a regulator of anti-inflammatory IL-10 response.

BACKGROUND: Sepsis remains a substantial risk after surgery or other trauma. Macrophage dysfunction, as a component of immune suppression seen during trauma and sepsis, appears to be one of the contributing factors to morbidity and mortality. However, whereas it is known that the ability of macrophages to present antigen and express major histocompatibility complex MHC class II molecules is decreased during sepsis, it is not known to what extent this is associated with the loss of co-stimulatory receptor expression. Our objectives in this study were, therefore, to determine if the expression o…

Prevention of graft-versus-host disease by induction of immune tolerance with ultraviolet B-irradiated leukocytes in H-2 disparate bone marrow donor.

Transfusions (Tx) of Ultraviolet B (UVB)-irradiated peripheral blood mononuclear leukocytes (MNL) have been shown to induce humoral immune tolerance to major histocompatability complex (MHC) antigens (Blood 88:4375, 1996). To determine whether cellular immune tolerance to MHC antigens can be induced by the same approach, transplantation of bone marrow and spleen cells from tolerant donors across the H-2 barrier was conducted to study its effect on prevention of graft-versus-host disease (GVHD). After immune tolerance induction by four weekly Tx of UVB-irradiated BALB/c (H-2(d)) peripheral bloo

Antileukocyte antibody in postpartum and renal transplant subjects. A comparison of capillary agglutination and lymphocytotoxicity reactions.

Sera were obtained from 48 gravida II prenatal and 211 multiparous nonpregnant females and examined for leukocyte antibodies comparing a standard lymphocytotoxicity (CY) test with capillary agglutination (CA). Antibody was detected in 41% of the samples in both groups but only CA tests were positive with approximately one-half of the prenatal and three-fourths of the multiparous specimens. Although, CA reactions, when accompanied by positive CY responses, usually correlated with HLA, no correlation with HLA, 5b, or the neutrophil antigens was determined for 35 of the 48 sera reacting only by C

Treatment of acute myeloid leukemia using CD3/CD123 bispecific antibody-engaged γδT cells in a mouse xenograft model.

BACKGROUND: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by dismal clinical outcomes. CD123, theαchain of the IL-3 receptor, is aberrantly overexpressed on AML blasts, representing a promising target for targeted immunotherapy. However, the clinical utility of CD123-targeted immunotherapies has been severely hampered by treatment-associated toxicities that disrupt normal hematopoietic homeostasis. In contrast, γδ T cells, endowed with the unique capacity to recognize antigens in a major histocompatibility complex (MHC)-independent manner, exert minimal cyt…

Positive effects of bile acids alleviating heat stress in laying hens by enhancing immunity via metabolome and transcriptome integration.

This experiment was aimed to investigate the effects of dietary supplementation with porcine-derived bile acids (BAs) on production performa … nate. Liver transcriptomics revealed 347 differentially expressed genes (DEGs), primarily involving major histocompatibility complex class I (MHC I), interleukin-2 receptor (IL-2R), transforming growth factor-β receptor (TGF-βR), and multivesicular body protein 12A (MVB12A). Spearman correlation analysis indicated that IgA was significantly positively correlated with 11,12,15-THE …

Expansion of IL-2-independent tumor-infiltrating lymphocytes through a feeder-free process: a preclinical study for solid tumors.

OBJECTIVE: Conventional tumor-infiltrating lymphocyte (TIL) therapy for solid tumors relies on high-dose interleukin-2 (IL-2) during expansi … through interferon-gamma (IFN-γ) release and real-time cell analysis (RTCA). HCQ-induced changes in major histocompatibility complex class I (MHC-I) and programmed death-ligand 1 (PD-L1) expression were assessed in tumor cell lines, and RTCA-based cytotoxicity was evaluated using T-cell receptor-engineered T cells (TCR-T cells). The in vivo efficacy of HCQ and PD-1 blockade separ …

Immune Cell-Specific Regulatory Gene Prioritization in Low Back Pain Using Single-Cell eQTL-Informed Mendelian Randomization and Colocalization.

OBJECTIVE: Low back pain (LBP) is a heterogeneous clinical pain condition, but the contribution of inherited immune cell-specific regulatory … 54 FDR-significant gene-cell type associations with LBP, of which 130 remained outside the extended major histocompatibility complex region. Among 114 MR-prioritized gene-cell type pairs evaluated by colocalization, 24 showed strong evidence of a shared genetic signal (PP.H4 ≥ 0.8), with most high-confidence signals located outside the MHC region. Recurrent candidates included C1 …

Mahuang Fuzi Xixin decoction attenuates allergic rhinitis by suppressing MHC-II-mediated antigen presentation in ovalbumin induced murine model.

BACKGROUND: Allergic rhinitis (AR) is a chronic condition that impairs daily life and imposes economic burdens. Mahuang Fuzi Xixin Decoction … he most prominently enriched. MFXD modulated splenic histopathology and spleen index, and decreased major histocompatibility complex class II (MHC-II) expression in both the nasal mucosa and spleen of AR mice. In vitro, MFXD diminished the antigen phagocytic capacity of lipopolysaccharide (LPS)-stimulated DC2.4 cells and lowered MHC-II and CD86 expression on both HNEpCs and DC2.4 …

Convergence in Pruning and Circadian Regulation in Obsessive-Compulsive Disorder and Allergic Diseases: Evidence From a Secondary Genome-Wide Analysis.

BACKGROUND: Obsessive-compulsive disorder (OCD) and allergic diseases co-occur far more often than expected, yet genome-wide genetic correla … ene set reached Bonferroni-corrected significance in allergic diseases (p = 6.75 × 10⁻⁵), driven by major histocompatibility complex (MHC) class I genes (HLA-B, HLA-A, HLA-C, TAP2), complement genes (C4A, C4B), and inflammatory regulators (NFKB1, RELA). The glutamatergic signalling set also survived the eight-set Bonferroni threshold (p = 0.005). The REACTOME Circadian Clock set …

Genetic liability to psoriasis predicts severe disease outcomes.

BACKGROUND: Psoriasis is a common inflammatory skin disease with heterogeneous presentation. Up to 30% of individuals have severe disease wi … iduals with psoriasis (21.7%) were classified as having severe disease. Genetic variants within the major histocompatibility complex (MHC) and the TNIP1 and IL12B psoriasis susceptibility loci were associated with severe disease at genome-wide significance (P < 5.0 × 10-8). Furthermore, a strong positive correlation was observed between psoriasis susceptibility and severity effec …

Herpes simplex virus type 1 impairs mucosal-associated invariant T cells.

UNLABELLED: Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that infects mucosal sites and adopts an arsenal of strategies to manipulate host immunity. Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes that recognize bacterial and fungal-derived vitamin B-related metabolites presented by major histocompatibility complex class I-related protein 1 (MR1). MAIT cells can also be activated in an MR1-independent manner via cytokine stimulation, predominantly by IL-12 and IL-18. MAIT cell alterations have been identified as being associated with a …

The clinical features, muscle pathology, and role of autophagy in anti-Ku-positive patients.

AIMS: This study aimed to examine the clinical and muscle histological characteristics of anti-Ku-positive patients. A preliminary investiga … or non-rimmed vacuoles (50%). Immunohistochemical (IHC) analysis revealed sarcolemma deposition of major histocompatibility complex class I (MHC-I) (83.3%) and MHC-II (83.3%), as well as predominant CD68-positive inflammatory infiltrates (66.7%). IHC for p62 revealed a sarcoplasmic punctate pattern (50%), along with a focal coarse staining pattern (50%) and occasional fine granu …

Factors that increase class I MHC expression may contribute to the development of immune checkpoint inhibitor-induced diabetes.

Immune checkpoint inhibitors (ICIs) have improved survival of patients with cancer, yet they pose risks of immune-related adverse events (ir … in additional ICI-treated patients and study effects of the NLRC5 variant on expression of class I major histocompatibility complex (MHC) antigen presentation genes.We assessed the prevalence of the C>T missense variant at chr16:57 025 515 (NLRC5Pro191Leu) in germline DNA from an additional 33 patients with ICI-DM and in patients with ICI-induced colitis (n=15), ICI-induced hypo …

Colorectal cancer organoids drive hypoxia, TGF-β, and patient-specific diversification of NK cell activation programs.

BACKGROUND: Colorectal carcinoma exhibits high heterogeneity, comprising subtypes that show poor efficacy of T cell-based immunotherapies, s … addition, we observed patient-specific differential PDO susceptibilities to NK cell-mediated lysis. Major histocompatibility complex class I deficiency and natural killer group 2, member D (NKG2D)-ligand expression on PDOs facilitated NK cell-mediated cytotoxicity, and induced phenotypic NK cell diversification related to activation and the acquisition of inflammation and tissue- …

Нейродегенерация и демиелинация в мультипликационном склерозном корде: клиническая, патологическая и 7T MRI Перспектива.

Основные выводы, сделанные в отношении лиц с множественным склерозом (МС) с постепенной инвалидностью двигателя, включают атрофию спинного мозга (SC), означающую необратимую аксонную потерю и демиелинированные повреждения СК. Цель этого исследования заключалась в выявлении нейродегенеративных изменений и оценке клинического воздействия и патологических характеристик повреждений СК. МЕТОДЫ: Было проведено перекрестное исследование с использованием посмертных сегментов шейного мозга в рамках программы скоростной аутопсии Кливлендской клиники MS. Включение включало близость к центру, отсутствие т

Совпадение в аннотации оригинала
BACKGROUND AND OBJECTIVES: Key findings in people with multiple sclerosis (MS) with progressive motor disability are spinal cord (SC) atroph … ative T2* relaxation times were correlated with myelin, axons, and activated microglia/macrophages (major histocompatibility complex II [MHCII]) using Tukey comparison of means and a linear mixed-effects model; T2* was correlated with clinical disease characteristics using Wilcoxon rank sum. RESULTS: The study included 40 MS cases (median age 58, female 55%) and 9 controls (medi …