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Results for “CSF immune cells”

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At least 19 recordsLinked to original sources
PubMed2026

DNA methylation landscape of cerebrospinal fluid cells in multiple sclerosis: an epigenome-wide association study.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which DNA methylation may link genetic and environmental risk factors. METHODS: We profiled genome-wide DNA methylation in cerebrospinal fluid (CSF) cells from people with MS (pwMS) and matched controls. Differentially methylated positions (DMPs) and regions (DMRs) were integrated with transcriptomic data, T-cell chromatin annotations, and pathway analyses. Protocadherin gamma (PCDHγ) expression was assessed in primary CD4+ T-cell subsets and confirmed by flow cytometry. FINDINGS: We identified 2710 DMPs and 4330 DMRs associating with genes that were enriched in immune signalling, adhesion and migration processes, and were accompanied by corresponding RNA changes. MS-associated methylation changes enriched in the cohesin chromatin-regulation pathway localised to T-cell regulatory regions, and this pathway included multiple protocadherin (PCDH) genes, which displayed consistent methylation and expression changes in CSF cells of pwMS compared to controls. PCDHγ cluster gene expression was detected in CD4+ T-cell subsets, and flow cytometry confirmed PCDHγ protein expression in peripheral blood T cells. Moreover, co-expression analysis suggests a role of PCDH genes in aryl hydrocarbon receptor (AHR) signalling. Protein-level validation showed fewer PCDHγ-positive CD4+ T cells in pwMS and activation-induced PCDHγ upregulation after T-cell stimulation. INTERPRETATION: DNA methylation changes in CSF resident cells reflect dysregulated T cell activation and migration in pwMS and suggest involvement of protocadherin molecules in MS pathogenesis. FUNDING: European Research Council, Swedish Research Council, Swedish Brain Foundation, Swedish MS Foundation, Knut and Alice Wallenberg Foundation, European Union and others.

Humans↗
PubMed1977

Cell-mediated cytotoxicity against measles virus in SSPE. I. Enhancement by antibody.

In patients with subacute sclerosing panencephalitis (SSPE) virus persistency has been explained by a blocking factor of specific cell-mediated immunity in SSPE serum and cerebrospinal fluid (CSF). In the present study the effect of SSPE serum and CSF on cell-mediated cytotoxicity against 51Cr-labeled allogenic measles virus-infected target cells was tested. Pretreatment of SSPE peripheral lymphoid cells by serum or CSF neither blocked nor increased measles-specific cytotoxicity when cells were subsequently tested in FCS containing tissue culture medium. However, killing activity was always enhanced after pretreatment of target cells or direct addition of serum or CSF to the cytotoxic assay. Enhancement was also observed with non-SSPE-derived measles antibodies. The effect was dependent on measles antibody concentrations. These results suggest that antibody-dependent killing by K cells is intact in patients with SSPE. It is possible that virus-infected brain cells are protected from an immune attack in vivo by antibody-induced antigenic modulation.

Antibodies, Viral↗
PubMed1977

Autoradiographic demonstration of proliferating cells in cerebrospinal fluid.

The proliferative activity of cells, isolated from 82 human CSF specimens, was examined by 3H-thymidine autoradiography. High labelling indices (LI) were found in acute viral meningitis (up to 8 per cent) and radiculitis (up to 6 per cent). CSF cell proliferation was also shown in the subacute stages of viral diseases and in other inflammatory processes (LI ranging from 0.5 per cent to 3 per cent). Most of the cells labelled from these CSF specimens were large lymphocytes, "lymphoid cells" and plasmacytes. Their presence in CSF is presumed to indicate an immune reaction. By the demonstration of a proliferative activity of these cells, aseptic inflammatory processes can be differentiated from "unspecific" pleocytosis. Because of a correlation between the LI of CSF cells and the stages of some inflammations, this method is suggested for an assessment of pregression or remission of chronic processes, e.g. "chronic meningitis" and multiple sclerosis. It can also be used in experimental research: the same type of mononuclear cells was labelled after having been cultured for 23 hours prior to the incubation with 3H-thymidine. Proliferating tumor cells as well as proliferating non-neoplastic mononuclear cells were demonstrated in CSF from various neoplastic diseases. In the clinical diagnosis of these processes, the method is of limited value. It proved very useful, however, for an assessment of the therapeutic effects of intrathecal cytostatic therapy. CSF specimens from non-inflammatory and non-neoplastic diseases regularly contained very few proliferating cells (LI: less than 0.1).

Autoradiography↗
PubMed2026

Reprogramming of TLR-Ferroptosis Signaling and Immunometabolic Pathways Overcomes Myeloid Suppression to Improve Checkpoint Blockade in Prostate Cancer.

UNLABELLED: The limited efficacy of immunotherapies in advanced prostate cancer stems from a tumor microenvironment (TME) in which myeloid-driven immune suppression, stromal remodeling, and metabolic barriers converge to limit antitumor immunity. In this study, we characterized the immunometabolic properties of an ultrasmall prostate-specific membrane antigen-targeting silica particle therapy as a first-in-class strategy to reprogram the Toll-like receptor (TLR)-ferroptosis axis in MYC-driven prostate cancer. As single agents, these particles suppressed lipid and steroid biosynthesis, disrupted lipid peroxidation control, and impaired nutrient flux, sensitizing tumors to ferroptosis. Coordinated redox remodeling, stromal reprogramming, and innate immune activation reversed myeloid suppression and promoted CD8+ T-cell infiltration. When combined with CSF-1R inhibition and immune checkpoint blockade, the particles suppressed tumor growth, extended survival beyond 100 days, and achieved up to 50% complete remission in MYC-overexpressing models. These findings position TLR-ferroptosis axis remodeling as a mechanistic blueprint for rational, particle-driven immunotherapies with broad translational potential in prostate cancer and other immunologically refractory malignancies. SIGNIFICANCE: Clinically validated, PSMA-targeted ultrasmall core-shell silica particles reprogram immunometabolic pathways via a TLR-ferroptosis axis, enabling tumor microenvironment remodeling and potentiating checkpoint blockade in prostate cancer, with translational implications for treatment-resistant disease.

Male↗
PubMed1979

[Isoelectric focusing and agar electrophoresis of the cerebrospinal fluid in neurologic patients].

Both isoelectric focusing and routine agar gel electrophoresis have been carried out on the CSF, and in some cases also on the corresponding serum, from 452 control subjects and patients with neurological diseases among whom cases with multiple sclerosis (MS) predominated. Comparison of the results confirms the superiority of electrofocusing over gel electrophoresis for the evaluation of oligoclonal immune reactions of the CNS. Over 90% of the MS patients showed discontinuous subfractionation of the gamma-globulins, mostly confined to the CSF, whereas with agar gel electrophoresis an identical effect could be seen only in about 60% of the same patients. Of special interest is the fact that by isoelectric focusing an additional 20% of MS patients whose gamma-globulin content, cell count and plasma cell findings in the CSF are within normal limits show oligoclonal CSF immune reactions. Thus, after appropriate screening by routine electrophoresis to reduce the number of analyses, the relatively laborious method of isoelectric focusing is an effective addition to the usual CSF investigations.

Cerebrospinal Fluid↗
PubMed1976

The possible local synthesis of antibodies to herpes simplex virus in normal cerebrospinal fluid.

We have used the technique of antibody mediated cell dependent immune lysis to examine paired samples of serum and CSF for antibody to herpes simplex virus. The 40 patients studied had no inflammatory disease of the nervous system, yet 20 of the CSF specimens did have antiviral antibody. This is an extremely sensitive technique for the detection of at least one type of antiviral antibody and "in vitro" is a very effective way of killing virus infected cells. There is no correlation between the level of antiviral antibody in the CSF with the total protein content, but the high CSF: serum antibody ratio in some subjects who are particularly susceptible to recurrent herpes infection raises the possibility that local stimulation and production of this antibody may occur.

Adult↗
PubMed2026

ER proteostasis failure in HYOU1 deficiency alters B cells, neutrophils, and interferon signalling.

Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic HYOU1 variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while HYOU1 transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis.

Journal Article↗
PubMed1978

Decreased lymphocyte transformation to vaccinia virus in multiple sclerosis.

Lymphocyte transformation to vaccinia virus was measured in multiple sclerosis (MS) patients and normal controls. There was a significant reduction of lymphocyte transformation to vaccinia virus in multiple sclerosis patients compared with the control group. In addition, a positive correlation existed between the degree of disability of the multiple sclerosis patients and the extent of lymphocyte transformation in the presence of vaccinia virus. There was no correlation between cell-mediated immunity to vaccinia virus and either serum or cerebrospinal fluid (CSF) antibody levels to vaccinia in multiple sclerosis patients or controls, all of whom had been previously vaccinated. In conjunction with other studies, all of whom had been previously vaccinated. In conjunction with other studies that have demonstrated elevated antibody titers to vaccinia virus in the CSF of multiple sclerosis patients, these results support the possibility that vaccinia virus may play a role in the pathogenesis of multiple sclerosis.

Adolescent↗
PubMed1976

Specific inhibitory factors of cellular immunity in children with subacute sclerosing panencephalitis.

Employing a 51Cr release cytotoxicity microassay, and using both measles-and SSPE-infected target cells, four patients with documented SSPE were evaluated for specific cellular and humoral immunity. Mononuclear leukocytes from SSPE patients and control subjects exhibited comparable cytotoxicity. Serum and CSF from these SSPE patients inhibited the cellular response to SSPE-infected cells but not to measles-infected cells. Moreover, fresh whole serum alone from control donors produced significant 51Cr release from both cell lines, whereas SSPE whole serum was effective only against measles-infected cells. CSF from an additional ten patients with SSPE was examined for inhibitory activity: seven of these completely blocked and one partially blocked cell-mediated cytotoxicity to SSPE-infected cells. Preliminary characterization of the serum inhibitory factor suggested that it is IgM or antigen-antibody complexes. These data also suggest antigenic differences between the SSPE and measles viruses.

Adolescent↗
PubMed1979

Studies on the humoral and cell-mediated immune response in a patient with Mollaret's meningitis.

A patient with Mollaret's meningitis with protracted course and a strong immune response within the central nervous system is described. The findings of IgG bands in agarose gel electrophoresis of CSF together with elevated CSF IgG index values are in accordance with intrathecal synthesis of IgG, possibly against an antigen persistent in the CNS. Subgrouping of CSF lymphocytes morphologically (B/T, active T cells) and functionally (stimulation with mitogens) showed that these cells differed from peripheral blood lymphocytes. A defect in the regulatory function of T cells may be responsible for the continuing pathologic process in Mollaret's meningitis.

Antibodies, Viral↗
PubMed1979

Studies on the kinetics of hemopoietic stem cells and immune responses to the hapten-carrier conjugate.

The correlation between the kinetics of hemopoietic stem cells and immune responses to the hapten-carrier conjugate was investigated. The numbers of both pluripotent stem cells (CFU-S) and myeloid stem cells (CFU-C) in the spleen from mice immunized with the hapten-carrier conjugate were significantly greater than those of the control and the activity of colony-stimulating factor (CSF) in the serum of these mice was markedly elevated. The supernatant of short-term incubation of splenic T lymphocytes from these mice, when stimulated with carrier protein, had high levels of both activities of CSF and helper T cell factors. The study by gel chromatography showed that these factors are similar m.w. substances of 35,000 to 45,000 daltons. But analysis by ion-exchange chromatography demonstrated that they do not have identical biochemical properties. The present studies suggest that biologically active factors produced by T cells stimulated with carrier protein may induce the enhancing effect on the proliferation and differentiation of hemopoietic stem cells and immune responses to the hapten-carrier conjugate.

Animals↗
PubMed1978

The immune response in human demyelinating diseases.

Lymphocytes present in the brain, meninges and cerebrospinal fluid (CSF) in multiple sclerosis (MS) are capable of synthesizing IgG. The CSF in MS contains more T-lymphocytes and fewer B-lymphocytes compared to blood. The reactivity of CSF lymphocytes in MS to T-cell mitogens and probably also to a combined B-and T-cell mitogen is absent or heavily reduced. This unresponsiveness of CSF lymphocytes may be a consequence of their previous activation. The blood lymphocytes in MS are not altered regarding distribution of B-and T-cells, nor regarding responsiveness to mitogens, when compared with healthy controls. An asynchronous synthesis of heavy and light immunoglobulin chains occurs within the CNS in many MS patients, giving rise to oligoclonal band patterns on electrophoresis and abnormal kappa/lambda light chain ratios of CSF. The synthesized immunoglobulins are most probably antibodies which may play a role in the pathogenesis and course of human demyelinating diseases. The brain must be regarded, from an immunological point of view, as a privileged site with its own immune system and its characteristic immune reactions, and future research concerning demyelinating diseases should, if possible, include investigations of these reactions.

Antibodies, Viral↗
PubMed1975

Motor neurone disease: an immunological study.

The state of the immune system, both humoral and cell-mediated, was evaluated in motor neurone disease (MND) patients. The data obtained for the MND patients were confronted with normal controls and a group of patients affected by nervous diseases not involving the immune system. Some differences were observed between MND patients and normal subjects, namely: increase of WBC and gamma-globulin in MND patients. However, such differences were not observed between MND patients and pathological controls, and therefore are probably due to a higher frequency of infectious complications in MND patients in respect to normal controls. The capacity of the immune system to respond to an adequate stimulus was normal, and no precipitating anti-CNS antibodies were detected in MND sera. Furthermore, no sex-linked differences were observed and the CSF abnormalities observed in 2 out of 16 MND patients were probably reflecting only destruction of CNS cells. The data are discussed in view of the possible pathogenetic mechanisms of MND.

Amyotrophic Lateral Sclerosis↗
PubMed1979

Aspects of cellular immunity in multiple sclerosis. Antigen-reactivity of lymphocytes and lymphokine activity.

Some new results of cell-mediated immunity in multiple slcerosis (MS) are presented, based on the determination of charge-changing lymphokines as products of antigen sensitive lymphocytes (C PAL), obtained by several forms of the electrophoretic mobility (EM) method. Lymphocytes from MS react to myelin basic protein (BP), the reactivity in other neurological diseases depending on the degree of destruction of nervous parenchyma. Applying a membrane-associated antigen from normal brain (NTA), positive reactivity of MS lymphocytes was obtained. Besides the usual determination of lymphokines in vitro the sensitive EM test allows the demonstration of lymphokine activities in vivo; i.e. in body fluids such as cerebrospinal fluid (CSF) and serum. In CSF of MS a high lymphokine activity was found. The differentiation of lymphokines and comparison between in vitro and in vivo activity were carried out. Moreover, a characteristic lymphokine pattern for MS with high activities in all regions of molecular weight, especially in the CSF, could be detected. On the basis of these findings, important also from the pathogenetic point of view, a diagnostic scheme for MS is suggested, consisting of a program of determination of the immuno-reactive CSF syndrome and some special procedures, including examination of lymphocyte reactivity.

Brain↗
PubMedDate not supplied

Unique aspects of central nervous system immunology.

In this review the authors discuss three immunologically unique aspects of the central nervous system (CNS). The first relates to whether the CNS is really an immunologically privileged site. Although still somewhat controversial, the answer to that question is that the CNS is, to a large extent, an immunologically privileged site. The second unique aspect of the CNS is the origin and significance of the microglial cell. Some microglial cells seem to originate from the systemic circulation, whereas other microglial cells seem to have a primary CNS origin. The function of the microglial cell is that of a macrophage. In addition it may play an important role in the immune response of the CNS. Present evidence suggests that the microglial cell can be classified as a lymphoreticular cell and as such is the only member of this cell type present in the CNS under normal circumstances. The final unique aspect of the central nervous system is the cerebrospinal fluid (CSF). Under normal circumstances this fluid is essentially acellular, and the only immunoglobulins present are those that are passively derived by diffusion from the systemic circulation. However, in pathological situations (i.e., demyelinating diseases, infections, and possibly even tumors) a local immune response occurs within the CNS and can result in the production of immunoglobulins. At present the detection of such local immune responses in CSF is predominately of diagnostic value only. However, these local CNS immune responses almost certainly play an important role in the pathogenesis of the diseases in which they occur.

Adult↗
PubMed1978

Varicella and acute cerebellar ataxia.

In two cases of varicella-associated cerebellar ataxia, varicella-zoster antigens in CSF cells were shown by an indirect immunofluorescent technique. Direct viral invasion in CNS disease complicating varicella plays an important part in pathogenesis and rules out a single immune-mediated mechanism.

Antigens, Viral↗
PubMed2026

Multi-omics profiling of cerebrospinal fluid in autoimmune encephalitis: insights into pathogenesis and therapeutic targets.

BACKGROUND: Autoimmune encephalitis (AIE) is a rare, severe inflammatory brain disease, with its pathogenesis not yet fully elucidated. This study aimed to characterize proteomic and metabolomic alterations in the cerebrospinal fluid (CSF) of AIE patients and identify potential therapeutic targets. METHODS: 65 consecutive AIE patients and age-matched concurrent controls were enrolled, respectively. Clinical characteristics, including blood and CSF laboratory findings, were compared between the two groups, and CSF samples were collected for multi-omics analysis. Differentially expressed proteins (DEPs) and metabolites (DEMs) between AIE patients and controls were identified using data-independent acquisition-based proteomics and targeted liquid chromatography-mass spectrometry-based metabolomics, followed by integrated multi-omics analysis. RESULTS: Compared with controls, AIE patients had lower levels of triglyceride and C1q, but higher HDL-CH levels, neutrophil counts, and eosinophil counts in blood. CSF leukocyte, erythrocyte, lymphocyte, and mononuclear cell counts were also elevated in AIE patients. Proteomic analysis identified 163 DEPs, with enrichment of 87 canonical pathways primarily associated with immune-inflammatory responses, neuronal-synaptic dysfunction, and cell signaling and metabolic pathways. Metabolomic analysis recognized 21 DEMs, predominantly amino acids, lipids, and carbohydrates, which were involved in lipid-carbohydrate metabolism and immune regulation. Integrated multi-omics analysis validated these findings and identified several potential therapeutic targets for AIE, including the IL6-STAT3 axis. CONCLUSIONS: Integrated multi-omics analysis systematically delineates cellular and molecular alterations underlying AIE. Immune-inflammatory response and lipid metabolism are pivotal in AIE progression and the IL6-STAT3 axis holds promise as a potential therapeutic target.

Humans↗
PubMed1977

Classification of cells in the cerebrospinal fluid. A review.

Comparative ultrastructural findings of meninges, ventricular ependyma and choroid plexus of mammals including man were summarized with the aim of a better understanding as to which cells can play a role as macrophages in the cerebrospinal fluid (CSF) cytology. Differences between phagocytic capacity of pial cells and arachnoid cells were emphasized. Comparative investigations showed that most of the cells in the CSF originate from the blood. Scanning electron microscopy of the subarachnoid space and cytological investigation of the CSF gave the result that haematogenous cells belong to the normal cell population of the subarachnoid space of normal individuals. These cells in the CSF react as their equivalents in the blood, that is, after confrontation with antigens the monocytes transform into macrophages, sometimes into multinucleated giant cells, the T and B lymphocytes transform into blast cells. On the basis of immunological and ultrastructural results, the classification of CSF cells in normal and pathological conditions has been proposed.

Animals↗