scholarly journals T Helper Cells: The Modulators of Inflammation in Multiple Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 482 ◽  
Author(s):  
Martina Kunkl ◽  
Simone Frascolla ◽  
Carola Amormino ◽  
Elisabetta Volpe ◽  
Loretta Tuosto
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Inflammatory Disorder ◽  
T Helper ◽  
Th Cells ◽  
Cytokines And Chemokines ◽  
Th Cell ◽  
The Central Nervous System ◽  
Cell Subpopulations

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by the progressive loss of axonal myelin in several areas of the central nervous system (CNS) that is responsible for clinical symptoms such as muscle spasms, optic neuritis, and paralysis. The progress made in more than one decade of research in animal models of MS for clarifying the pathophysiology of MS disease validated the concept that MS is an autoimmune inflammatory disorder caused by the recruitment in the CNS of self-reactive lymphocytes, mainly CD4+ T cells. Indeed, high levels of T helper (Th) cells and related cytokines and chemokines have been found in CNS lesions and in cerebrospinal fluid (CSF) of MS patients, thus contributing to the breakdown of the blood–brain barrier (BBB), the activation of resident astrocytes and microglia, and finally the outcome of neuroinflammation. To date, several types of Th cells have been discovered and designated according to the secreted lineage-defining cytokines. Interestingly, Th1, Th17, Th1-like Th17, Th9, and Th22 have been associated with MS. In this review, we discuss the role and interplay of different Th cell subpopulations and their lineage-defining cytokines in modulating the inflammatory responses in MS and the approved as well as the novel therapeutic approaches targeting T lymphocytes in the treatment of the disease.

scholarly journals Role of the major histocompatibility complex in T cell activation of B cell subpopulations. A single monoclonal T helper cell population activates different B cell subpopulations by distinct pathways.

1982 ◽  
Vol 156 (2) ◽  
pp. 350-360 ◽  
Author(s):  
Y Asano ◽  
M Shigeta ◽  
C G Fathman ◽  
A Singer ◽  
R J Hodes
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cell Interaction ◽  
T Helper Cell ◽  
T Helper ◽  
Th Cells ◽  
Histocompatibility Complex ◽  
Th Cell ◽  
Cell Subpopulations

It has recently been demonstrated that the Lyb-5+ and Lyb-5- B cell subpopulations differ in their requirements for major histocompatibility complex (MHC)-restricted activation by T helper (TH) cells. To determine whether these MHC-restricted and -unrestricted pathways of B cell activation result from differences in the participating TH cell populations or reflect differences exclusively in the responding B cell subpopulations, experiments were carried out using cloned TH cells for in vitro antibody responses to trinitrophenyl-keyhole limpet hemocyanin. The same cloned T helper cells were able to activate both CBA/N (Lyb-5-) B cells and CBA/CaHN (Lyb-5+ + Lyb-5-) B cells under different experimental conditions. The activation of Lyb-5-B cells by cloned T helper cells required both MHC-restricted TH cell-B cell interaction and carrier-hapten linkage. In contrast, the activation of Lyb-5+ B cells required only MHC-restricted T helper cell interaction with accessory cells, while T-B interaction was MHC unrestricted and did not require carrier-hapten linkage. Thus, the differences in activation requirements observed for the Lyb-5- and Lyb-5+ B cell subsets do not result from differences in the TH cell populations activating these B cells, but rather reflect differences in the ability of these B cells to respond to signals from the same TH cells.

scholarly journals Multiple Sclerosis Biomarker Discoveries by Proteomics and Metabolomics Approaches

2021 ◽  
Vol 16 ◽  
pp. 117727192110133
Author(s):  
Ameneh Jafari ◽  
Amirhesam Babajani ◽  
Mostafa Rezaei-Tavirani
Keyword(s):  
Multiple Sclerosis ◽  
Complex Disease ◽  
Biomarker Discovery ◽  
Response To Treatment ◽  
Inflammatory Disorder ◽  
Protein Marker ◽  
Complex Disorders ◽  
New Information ◽  
The Central Nervous System ◽  
Monitoring Treatment

Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system (CNS) resulting in demyelination and axonal loss in the brain and spinal cord. The precise pathogenesis and etiology of this complex disease are still a mystery. Despite many studies that have been aimed to identify biomarkers, no protein marker has yet been approved for MS. There is urgently needed for biomarkers, which could clarify pathology, monitor disease progression, response to treatment, and prognosis in MS. Proteomics and metabolomics analysis are powerful tools to identify putative and novel candidate biomarkers. Different human compartments analysis using proteomics, metabolomics, and bioinformatics approaches has generated new information for further clarification of MS pathology, elucidating the mechanisms of the disease, finding new targets, and monitoring treatment response. Overall, omics approaches can develop different therapeutic and diagnostic aspects of complex disorders such as multiple sclerosis, from biomarker discovery to personalized medicine.

scholarly journals A Signal Transducer and Activator of  Transcription (Stat)4-independent Pathway for the Development of  T Helper Type 1 Cells

1998 ◽  
Vol 188 (6) ◽  
pp. 1191-1196 ◽  
Author(s):  
Mark H. Kaplan ◽  
Andrea L. Wurster ◽  
Michael J. Grusby
Keyword(s):  
Delayed Type Hypersensitivity ◽  
Th2 Cells ◽  
Signal Transducer ◽  
T Helper ◽  
Th1 Cell ◽  
Th Cells ◽  
Th Cell ◽  
Ifn Γ

The differentiation of T helper (Th) cells is regulated by members of the signal transducer and activator of transcription (STAT) family of signaling molecules. We have generated mice lacking both Stat4 and Stat6 to examine the ability of Th cells to develop in the absence of these two transcription factors. Stat4, Stat6−/− lymphocytes fail to differentiate into interleukin (IL)-4–secreting Th2 cells. However, in contrast to Stat4−/− lymphocytes, T cells from Stat4, Stat6−/− mice produce significant amounts of interferon (IFN)-γ when activated in vitro. Although Stat4, Stat6−/− lymphocytes produce less IFN-γ than IL-12–stimulated control lymphocytes, equivalent numbers of IFN-γ–secreting cells can be generated from cultures of Stat4, Stat6−/− lymphocytes activated under neutral conditions and control lymphocytes activated under Th1 cell–promoting conditions. Moreover, Stat4, Stat6−/− mice are able to mount an in vivo Th1 cell–mediated delayed-type hypersensitivity response. These results support a model of Th cell differentiation in which the generation of Th2 cells requires Stat6, whereas a Stat4-independent pathway exists for the development of Th1 cells.

scholarly journals Impact of Multiple Sclerosis on Infertility and Impact of Infertility Treatments on Multiple Sclerosis Relapses in Slovenia: Medical Outline, Legal and Ethical Outcomes

2020 ◽  
Vol 13 (2) ◽  
pp. 153-172
Author(s):  
Eda Vrtačnik Bokal ◽  
Urban Vrtačnik
Keyword(s):  
Multiple Sclerosis ◽  
Detrimental Effect ◽  
Interdisciplinary Approach ◽  
Reproductive Period ◽  
Inflammatory Disorder ◽  
Infertility Treatments ◽  
Legal Outcomes ◽  
Significant Disability ◽  
The Central Nervous System

Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system. It is common in the reproductive period and can lead to infertility and significant disability. The treatment on multiple sclerosis is recently more successful and enables better quality of life, therefore rising hope and desire for future parents, also in terms of successful infertility treatments. In this context, the couples should be managed concerning the detrimental effect of the disease itself on fertility, detrimental effect of the drugs used for treatment on gonads and in terms of the implementation of drugs used for ovarian stimulation and their impact on the basic disease (MS). The article finds solutions on the legal outcomes in situations where infertility treatments may negatively impact the progress of MS, as well as the solutions on how to (successfully) provide infertility treatments to the patients with MS. It proposes interdisciplinary approach between gynaecologists and neurologists to perform required weighing of benefits and risks (burdens), deriving from specific action or treatment, whereas for the patients who shall not undergo infertility treatments due to their medical status, related to MS, it proposes storage of gametes under conditions, set by the law.

scholarly journals H-2-controlled suppression of T cell response to lactate dehydrogenase B. Characterization of the lactate dehydrogenase B suppressor pathway.

1982 ◽  
Vol 156 (3) ◽  
pp. 822-833 ◽  
Author(s):  
C N Baxevanis ◽  
N Ishii ◽  
Z A Nagy ◽  
J Klein
Keyword(s):  
Lactate Dehydrogenase ◽  
T Cell ◽  
Cell Response ◽  
Cell Types ◽  
T Cell Response ◽  
T Helper ◽  
Th Cells ◽  
Th Cell ◽  
Antigen Presenting

We characterized the cell types involved in the H-2-controlled suppression of T cell response to lactate dehydrogenase B (LDHB). The suppressor effector (Tse) was found to be an Lyt-1+2+, J+ cell that recognizes antigen together with Ek molecules of antigen-presenting cells (APC). To become functional, the Tse cell requires a second signal from a nonspecific, Lyt-1+2-, J+ suppressor-inducer (Tsi) cell. The Tsi-Tse interaction is not subject to any genetic restriction. The target cell of suppression is an Lyt-1+2-, J- (most likely T helper [Th]) cell that recognizes LDHB in the context of A molecules on APC. The suppression is manifested in inhibition of the antigen-specific, A-restricted proliferation of Th cells. The interaction between Tse and Th is restricted by the A region of the H-2 complex. Because this restriction is determined by the receptor of Th cells, the mechanism of Th-Tse interaction most likely involves a concomitant recognition of LDHB and A region-controlled molecules by Th cells on the surface of Tse cells.

Neuromyelitis Optica

2017 ◽  
Author(s):  
Teri L. Schreiner ◽  
Jeffrey L. Bennett
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Water Channel ◽  
Transverse Myelitis ◽  
Inflammatory Disorder ◽  
The Central Nervous System

Neuromyelitis optica (NMO), or Devic’s disease is an inflammatory disorder of the central nervous system that preferentially affects the optic nerves and spinal cord. Initially considered a variant of multiple sclerosis (MS), NMO is now clearly recognized to have distinct clinical, radiographic, and pathologic characteristics. Historically, the diagnosis of NMO required bilateral optic neuritis and transverse myelitis; however, the identification of a specific biomarker, NMO-IgG, an autoantibody against the aquaporin-4 (AQP4) water channel, has broadened NMO spectrum disease to include patients with diverse clinical and radiographic presentations. This chapter addresses the diagnosis, pathophysiology, and management of the disease.

scholarly journals Neuron-specific SALM5 limits inflammation in the CNS via its interaction with HVEM

2016 ◽  
Vol 2 (4) ◽  
pp. e1500637 ◽  
Author(s):  
Yuwen Zhu ◽  
Sheng Yao ◽  
Mathew M. Augustine ◽  
Haiying Xu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Virus Entry ◽  
Neuronal System ◽  
Specific Monoclonal Antibody ◽  
Autoimmune Encephalomyelitis ◽  
Mouse Experimental Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Functional Receptor ◽  
Experimental Autoimmune

The central nervous system (CNS) is an immune-privileged organ with the capacity to prevent excessive inflammation. Aside from the blood-brain barrier, active immunosuppressive mechanisms remain largely unknown. We report that a neuron-specific molecule, synaptic adhesion-like molecule 5 (SALM5), is a crucial contributor to CNS immune privilege. We found that SALM5 suppressed lipopolysaccharide-induced inflammatory responses in the CNS and that a SALM-specific monoclonal antibody promoted inflammation in the CNS, and thereby aggravated clinical symptoms of mouse experimental autoimmune encephalomyelitis. In addition, we identified herpes virus entry mediator as a functional receptor that mediates SALM5’s suppressive function. Our findings reveal a molecular link between the neuronal system and the immune system, and provide potential therapeutic targets for the control of CNS diseases.

scholarly journals A Pathogenic Role for Myelin-Specific Cd8+ T Cells in a Model for Multiple Sclerosis

2001 ◽  
Vol 194 (5) ◽  
pp. 669-676 ◽  
Author(s):  
Eric S. Huseby ◽  
Denny Liggitt ◽  
Thea Brabb ◽  
Bryan Schnabel ◽  
Claes Öhlén ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Demyelinating Disease ◽  
Clinical Symptoms ◽  
Autoimmune Encephalomyelitis ◽  
Effector Cells ◽  
Cns Autoimmunity ◽  
The Central Nervous System

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by plaques of infiltrating CD4+ and CD8+ T cells. Studies of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, focus on the contribution of CD4+ myelin-specific T cells. The role of CD8+ myelin-specific T cells in mediating EAE or MS has not been described previously. Here, we demonstrate that myelin-specific CD8+ T cells induce severe CNS autoimmunity in mice. The pathology and clinical symptoms in CD8+ T cell–mediated CNS autoimmunity demonstrate similarities to MS not seen in myelin-specific CD4+ T cell–mediated EAE. These data suggest that myelin-specific CD8+ T cells could function as effector cells in the pathogenesis of MS.

scholarly journals Follicular lymphoma tumor–infiltrating T-helper (TH) cells have the same polyfunctional potential as normal nodal TH cells despite skewed differentiation

Blood ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3591-3602 ◽  
Author(s):  
Shannon P. Hilchey ◽  
Alexander F. Rosenberg ◽  
Ollivier Hyrien ◽  
Shelley Secor-Socha ◽  
Matthew R. Cochran ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Follicular Lymphoma ◽  
Critical Role ◽  
Cell Receptor ◽  
Effector Memory ◽  
T Helper ◽  
Th Cells ◽  
Lineage Differentiation ◽  
Th Cell

Abstract The follicular lymphoma (FL) T-cell microenvironment plays a critical role in the biology of this disease. We therefore determined the lineage, differentiation state, and functional potential of FL-infiltrating CD4+ T-helper cells (TH) compared with reactive and normal lymph node (NLN) TH cells. Relative to NLNs, FL cells have decreased proportions of naive and central memory but increased proportions of effector memory TH cells. We further show differences in the distribution and anatomical localization of CXCR5+ TH populations that, on the basis of transcription factor analysis, include both regulatory and follicular helper T cells. On Staphylococcus enterotoxin-B stimulation, which stimulates T cells through the T-cell receptor, requires no processing by APCs, and can overcome regulator T cell-mediated suppression, the proportion of uncommitted primed precursor cells, as well as TH2 and TH17 cells is higher in FL cells than in reactive lymph nodes or NLNs. However, the proportion of TH1 and polyfunctional TH cells (producing multiple cytokines simultaneously) is similar in FL cells and NLNs. These data suggest that, although TH-cell differentiation in FL is skewed compared with NLNs, FL TH cells should have the same intrinsic ability to elicit antitumor effector responses as NLN TH cells when tumor suppressive mechanisms are attenuated.

scholarly journals Disrupted microglial iron homeostasis in progressive multiple sclerosis

2021 ◽  
Author(s):  
Dimitry Ofengeim ◽  
Jonathan D Proto ◽  
Mindy Zhang ◽  
Sean Ryan ◽  
Xinting Yao ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Iron Homeostasis ◽  
Clinical Symptoms ◽  
Cell Types ◽  
Progressive Multiple Sclerosis ◽  
Post Mortem Brain ◽  
The Central Nervous System ◽  
Single Nucleus ◽  
Multiple Cell ◽  
Chronic Autoimmune Disease

Multiple Sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS). Despite therapies that reduce relapses, many patients eventually develop secondary progressive MS (SPMS), characterized by ongoing and irreversible neurodegeneration and worsening clinical symptoms. Microglia are the resident innate immune cells of the CNS. While the cellular and molecular determinants of disability progression in MS remain incompletely understood, they are thought to include non resolving microglial activation and chronic oxidative injury. In this study, our aim was to better characterize microglia in SPMS tissues to identify disease-related changes at the single cell level. We performed single nucleus RNA-seq (snRNA-seq) on cryopreserved post-mortem brain cortex and identified disease associated changes in multiple cell types and in particular distinct SPMS enriched microglia subsets. When compared to the cluster most enriched in healthy controls (i.e. homeostatic microglia), we found a number of SPMS-enriched clusters with transcriptional profiles reflecting increased oxidative stress and perturbed iron homeostasis. Using histology and RNA-scope, we confirmed the presence of iron accumulating, ferritin-light chain (FTL)-expressing microglia in situ. Among disease-enriched clusters, we found evidence for divergent responses to iron accumulation and identified the antioxidant enzyme GPX as a key fate determinant. These data help elucidate processes that occur in progressive MS brains, and highlight novel nodes for therapeutic intervention.

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