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Hemophagocytic Lymphohistiocytosis: an Under-recognized and Life-threatening Condition.

Diagnosis of hemophagocytic lymphohistiocytosis is a challenge in Nepal because of limited resources and the high prevalence of tropical febrile illness mimicking hemophagocytic lymphohistiocytosis. We retrospectively reviewed medical records of 21 patients who were diagnosed with hemophagocytic lymphohistiocytosis from 2010 to 2015 at a single center in Nepal. Two patients had a mutation in their perforin gene and underwent successful haploidentical stem cell transplantation. Marrow hemophagocytosis was found only in 57% of the patients. Five patients had hematological malignancy and were tre…

Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies.

Muscle cell death in polymyositis is induced by CD8+ cytotoxic T lymphocytes. We hypothesized that the injured muscle fibers release pro-inflammatory molecules, which would further accelerate CD8+ cytotoxic T lymphocytes-induced muscle injury, and inhibition of the cell death of muscle fibers could be a novel therapeutic strategy to suppress both muscle injury and inflammation in polymyositis. Here, we show that the pattern of cell death of muscle fibers in polymyositis is FAS ligand-dependent necroptosis, while that of satellite cells and myoblasts is perforin 1/granzyme B-dependent apoptosis…

Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1.

Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunologic … us-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175-189 or POMT1675-689. Moreover, anti-POMT1 serum autoantibodies are increased in Pan …

CD4+ T cells persist for years in the human small intestine and display a TH1 cytokine profile.

Studies in mice and humans have shown that CD8+ T cell immunosurveillance in non-lymphoid tissues is dominated by resident populations. Whet … action produced IL-17. Interestingly, a fraction of intestinal CD4+ T cells produced granzyme-B and perforin after activation. Together, we show that the intestinal CD4+ T-cell compartment is dominated by resident populations that survive for more than 1 year. This finding is of high relevance for the development of oral vaccines and therapies for diseases …

A molecular signature for CD8+ T cells from visceral leishmaniasis patients.

CD8+ T-cell function is compromised in chronic diseases such as visceral leishmaniasis (VL). However, little is known about the changes in g … molecules, including LAG-3, TIM-3 and CTLA-4, cytolytic molecules, such as granzymes A, B and H and perforin, as well as SOCS3, STAT1, JAK2 and JAK3 cytokine signalling genes were found to be increasingly expressed by VL patient CD8+ T cells. Additional studies confirmed increased expression of the inhibitory receptors LAG3 and TIM3 on VL patient CD8+ T ce …

Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells.

Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysp … eripheral absolute neutrophil count, and hemoglobin concentration. Furthermore, expression rates of perforin and granzyme B in BM CD3+CD8+ cells (cytotoxic T lymphocyte, CTL) positively correlated with levels of IL-17 but negatively correlated with BM blast percentage and could be significantly increased after stimulation with human recombinant IL-17 (rhIL …

Glioma cell-derived placental growth factor induces regulatory B cells.

Tumor specific immune regulatory cells play an important role in the pathogenesis of glioma. The mechanisms have not been fully understood y … to protein extracts of glioma tissue to suppress the CD8(+) T cell proliferation and the release of perforin and granzyme B. We conclude that glioma cell-released PlGF can induce Bregs to suppress CD8(+) T cell activities.

Chapter 28: Classification of hypersensitivity reactions.

The original Gell and Coomb's classification categorizes hypersensitivity reactions into four subtypes according to the type of immune respo … istent asthma and allergic rhinitis); type IVc is cytotoxic CD8(+) T lymphocyte with involvement of perforin-granzme B in apoptosis (Stevens-Johnson syndrome and toxic epidermal necrolysis); type IVd is T-lymphocyte-driven neutrophilic inflammation (pustular psoriasis and acute generalized exanthematous pustulosis). Some diseases have multiple types of imm …

Haemophagocytic lymphohistiocytosis: a case series from Mumbai.

A retrospective review of ten patients (8 girls, 2 boys) admitted over a 9-month period with haemophagocytic lymphohistiocytosis (HLH) is presented. Presenting features included fever and hepatosplenomegaly (10), bleeding manifestations (7), lymphadenopathy (4), skin rash (4), shock (4), jaundice (3), CNS disorder (3), renal failure (2) and arthritis (2). Three infants had familial HLH (FHL) while the other seven patients had acquired (secondary) HLH. Two patients with FHL had very low perforin levels (0 and 0.05%). There was secondary HLH owing to systemic onset juvenile idiopathic arthritis …

Angeborene hämophagozytische Lymphohistiozytose (HLH).

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal immune disorder characterized by uncontrolled lymphocyte- and macrophage-activation. The resulting hypercytokinemia and cell infiltration of organs lead to the clinical and laboratory features of HLH. Viral infections and other triggers can induce both, inherited and acquired forms of HLH. Disease-causing mutations in the genes encoding perforin (PRF1, FHL2), munc13-4 (UNC13D, FHL3), syntaxin 11 (STX11, FHL4), and munc18-2 (UNC18-2/STXBP2, FHL5) have been previously identified in Familial Hemophagocyic Lymphohistiocytosis (FHL), w…

Визуальная демонстрация вирусной памяти по гепатиту С CD8(+) расширение Т-клеток у пациентов с острым гепатитом С.

Гепатит C-вирус (HCV) CD8(+)T клеток в периферийных моноядерных клетках крови (PBMC) у пациентов, инфицированных ВКВ, был количественно проанализирован с помощью цитометрии потока с помощью эпитопного тетрамерного комплекса HLA-B*3501-HCV. В хроническом гепатите С тетрамер(+)CD8(+) Т были обнаружены на частотах от 0,05% до 0,12% от общего числа CD8(+)T клеток. Количество тетрамерных (+) CD8(+) Т клеток в острой фазе PBMC у пациентов с острым гепатитом C было примерно в 3-5 раз выше, чем у тех же пациентов и у пациентов с хроническим гепатитом C. Расширение тетрамер(+)CD8(+) Т клеток в PBMC от

Совпадение в аннотации оригинала
Hepatitis C virus (HCV)-specific CD8(+) T cells in peripheral blood mononuclear cells (PBMCs) from patients infected with HCV were quantitat … atitis C did not predominantly express this phenotype. These tetramer(+)CD8(+) T cells did not have perforin in their cytoplasma. The present study visually showed that a high number of circulating HCV-specific CD8(+) T cells in acute phase PBMCs from patients with acute hepatitis C are mostly memory T cells.

[Familial hemophagocytic lymphohistiocytosis: diagnosis, treatment and pathophysiological mechanisms].

Familial hemophagocytic lymphohistiocytosis (FHL) is an invariably fatal disease typically seen in infancy and early childhood, with a media … evious suggestions that FHL may be caused by a deficiency in apoptosis were recently confirmed when perforin gene defects were described, which may well explain the disastrous lymphohistiocytic accumulation and subsequent T-cell activation.

Analysis of the tumor reactivity of autologous TILs and allogeneic γδ T cells via tumor organoid-immune cell coculture.

BACKGROUND: The efficacy of conventional αβ T cell-based immunotherapies is often limited by tumor immune evasion. γδ T cells can bypass the … track BCO infiltration and apoptosis over 24 hours. Secreted effector molecules (IFN-γ, granzyme B, perforin) were measured from coculture supernatants using a cytometric bead array. RESULTS: Baseline analysis revealed that γδ T cells represent the most reactive subset within expanded TILs, with 12.3% expressing CD137 compared to 3.49% of CD8+ T cells (p = …

[Type IV of hypersensitivity and its subtypes].

Type IV of hypersensitivity reaction is usually manifested in the skin in different clinical pattern. According to traditional Gell and Coom … yte apoptosis, a consequence of high CD8+ T-cell involvement and the molecular cytotoxicity of Fas, perforin and granzyme B. Pustular exanthema reactions are stimulated via the T-cell release of 11-8 and granulocyte-monocyte colony-stimulatig factor (GM-CSF). For the better understanding of these inflammatory cascades deleted type IV of hypersensitivity re …

Single-nucleus transcriptomics of an engineered pig model reveals microglia-T cell interactions driving Huntington's disease neurodegeneration.

Immune cell infiltration into the central nervous system is increasingly recognized as a driver of neurodegeneration, yet its role in Huntin … state that secretes chemokine ligand eight, recruiting cytotoxic CD8-positive T cells that release perforin and granzyme, thereby accelerating neuronal loss. Functional experiments confirmed the pathogenic role of chemokine ligand eight and demonstrated that its neutralization mitigates neurodegeneration. These findings uncover a species-dependent immune …

Platycodon grandiflorus-Derived Nanovesicles Sensitize Gastric Cancer to T Cell Killing via Ferroptosis-Driven Membrane Mechanical Remodeling.

Plant-derived nanovesicles have emerged as promising natural nanotherapeutics for cancer treatment, yet whether they can overcome the intrin … mitant increases in plasma membrane tension and cellular stiffness during ferroptosis, facilitating perforin pore formation and enhancing the susceptibility of gastric cancer cells to cytotoxic T-cell-mediated killing. Collectively, these findings establish a mechanistic link between ferroptosis-driven membrane mechanical remodeling and tumor immune suscep …

Latent Neoehrlichia mikurensis Infections May Be Reactivated in Patients With B-Cell Lymphomas Treated With Rituximab.

The intracellular, tick-borne bacterium Neoehrlichia (N.) mikurensis can cause neoehrlichiosis in patients with compromised B-cell defences, … ll suppression. All eight patients who were infected with N. mikurensis had N. mikurensis-specific, perforin-expressing Th1 and CD8+ T-cell populations with up-regulation of CXCL10 and IFN-γ, in contrast to the noninfected lymphoma patients who lacked these T-cell subsets. The infected lymphoma patients also had expanded γδ T-cell populations. This study s …

Methods for Probing NK Cell Surveillance of Antigen Presentation.

Natural killer (NK) cells are critical components of the innate immune system, capable of rapidly identifying and eliminating virus-infected and tumor cells without prior antigen sensitization. This rapid cytotoxic response is regulated by a balance between activating and inhibitory receptor signals, a mechanism known as "missing self." Inhibitory receptors recognize HLA class I molecules, preventing unwanted activation against healthy cells, while activating receptors detect stress-induced ligands on abnormal cells, triggering the release of perforin and granzyme B.Recent evidence shows that …

Molecular architecture and targeted killing mechanisms of T cell immune synapses in oral lichen planus.

OBJECTIVE(S): This review focuses on the formation, molecular composition, and functional dynamics of T cell immune synapses within oral lic … ignaling events, cytoskeletal reorganization, and polarized delivery of effector molecules (notably perforin and granzymes) that underpin this specific cytotoxicity. Furthermore, potential therapeutic strategies aimed at disrupting critical nodes within immune synapse assembly and function are evaluated. CONCLUSIONS: By integrating current knowledge, this …

Low-dose radiation by radiopharmaceutical therapy enhances GD2 TRAC-CAR T cell efficacy in localized neuroblastoma.

Chimeric antigen receptor (CAR) T cells have limited efficacy against solid tumors including neuroblastoma. Here, we evaluated whether low-d … on. Irradiation of neuroblastoma before GD2 TRAC-CAR T cells enhanced the release by CAR T cells of perforin, granzyme B, tumor necrosis factor-α, and interleukin-7 while abrogating transforming growth factor-β1. Low-dose RPT up-regulated the death receptor Fas on neuroblastoma, potentially enabling CAR-independent killing. This suggests that low-dose RPT …