CHAPTER 9: Immunology of TBEV-Infections

Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. Natural killer (NK) cells and T cells are activated during the second (meningo-encephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.

Chapter 9: Immunology of TBEV-Infection

Tick-borne encephalitis - The Book ◽

10.33442/978-981-14-0914-1_9 ◽

2019 ◽

Author(s):

Sara Gredmark-Russ ◽

Renata Varnaite

Keyword(s):

Central Nervous System ◽

T Cells ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Nk Cells ◽

Peripheral Blood ◽

Sample Collection ◽

Tick Borne Encephalitis ◽

Viral Infectious Disease ◽

• Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). • TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. • Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. • The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. • Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. • Natural killer (NK) cells and T cells are activated during the second (meningoencephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. • Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.

TGF-β in Mice Ameliorates Experimental Autoimmune Encephalomyelitis in Regulating NK Cell Activity

Cell Transplantation ◽

10.1177/0963689719852354 ◽

2019 ◽

Vol 28 (9-10) ◽

pp. 1155-1160 ◽

Cited By ~ 3

Author(s):

J. Xu ◽

Y. Wang ◽

H. Jiang ◽

M. Sun ◽

J. Gao ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

T Cells ◽

Nervous System ◽

Experimental Autoimmune Encephalomyelitis ◽

Nk Cells ◽

Nk Cell ◽

Autoimmune Encephalomyelitis ◽

Experimental Autoimmune

Multiple sclerosis is a disease characterized by inflammation and demyelination located in the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is the most common animal model for multiple sclerosis (MS). Although the roles of T cells in MS/EAE have been well investigated, little is known about the functions of other immune cells in the neuroinflammation model. Here we found that an essential cytokine transforming growth factor β (TGF-β) which could mediate the differentiation of Th17/regulatory T cells was implicated in the natural killer (NK) cells’ activity in EAE. In EAE mice, TGF-β expression was first increased at the onset and then decreased at the peak, but the expressions of TGF-β receptors and downstream molecules were not affected in EAE. When we immunized the mice with MOG antigen, it was revealed that TGF-β treatment reduced susceptibility to EAE with a lower clinical score than the control mice without TGF-β. Consistently, inflammatory cytokine production was reduced in the TGF-β treated group, especially with downregulated pathogenic interleukin-17 in the central nervous system tissue. Furthermore, TGF-β could increase the transcription level of NK cell marker NCR1 both in the spleen and in the CNS without changing other T cell markers. Meanwhile TGF-β promoted the proliferation of NK cell proliferation. Taken together, our data demonstrated that TGF-β could confer protection against EAE model in mice through NK cells, which would be useful for the clinical therapy of MS.

IL-18 Directs Autoreactive T Cells and Promotes Autodestruction in the Central Nervous System Via Induction of IFN-γ by NK Cells

The Journal of Immunology ◽

10.4049/jimmunol.165.6.3099 ◽

2000 ◽

Vol 165 (6) ◽

pp. 3099-3104 ◽

Cited By ~ 123

Author(s):

Fu-Dong Shi ◽

Kiyoshi Takeda ◽

Shizuo Akira ◽

Nora Sarvetnick ◽

Hans-Gustaf Ljunggren

Keyword(s):

Central Nervous System ◽

T Cells ◽

Nervous System ◽

Nk Cells ◽

Autoreactive T Cells ◽

Ifn Γ

Successful Treatment with Intrathecal Tocilizumab(IL-6 antibody) for 2 Cases of Graft-Versus Host Disease of the Central Nervous System after a Second Allogeneic HSCT from Haploidentical Donor

Blood ◽

10.1182/blood-2018-99-117725 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5730-5730

Author(s):

Ruirui Gui ◽

Juanjuan Zhao ◽

Yingling Zu ◽

Lu Han ◽

Yanli Zhang ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Cell Transplantation ◽

Graft Versus Host Disease ◽

Peripheral Blood ◽

Intrathecal Injection ◽

Graft Versus Host ◽

Hematopoietic Recovery ◽

Abstract Graft-versus-host disease (GVHD) of central nervous system (CNS) is a rare complication after allogeneic hematopoietic cell transplantation (allo-HSCT), which is easily misdiagnosed and has limited treatment and poor efficacy. In this study, we reported two children(1 case of severe aplastic anemia and 1 case of acute myeloid leukemia) who were subjected to the secondary haploid hematopoietic stem cell transplantation of another door after the first implantation failure. Two patients developed epileptic seizures during hematopoietic recovery. Peripheral blood and cerebrospinal fluid cytokines were detected and diagnosed as acute GVHD in the central nervous system. The cytokine elevation is mainly IL-6(IL-6 level in peripheral blood was 2276.25 pg/ml, and in cerebrospinal fluid was 2353.89pg/ml of case 1). We administered multiply consecutive plasmapheresis, intravenous infusion of tocilizumab combined with intrathecal injection of tocilizumab and dexamethasone. The epileptic symptoms of 2 cases are effectively controlled after the first dose. The IL-6 levels in peripheral blood and cerebrospinal fluid of both patients decreased significantly after 4(IL-6 level in peripheral blood was 6.74 pg/ml, and in cerebrospinal fluid was 195.72pg/ml of case 1) and 5 doses, respectively. Central nervous system aGVHD is prone to hematopoietic recovery after secondary transplantation; intrathecal injection of tocilizumab is safe and effective in the treatment of central nervous system aGVHD with elevated IL-6 mainly, which is worth further exploring. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Relapse of multiple sclerosis in a patient retaining CCR7-expressing T cells in CSF under fingolimod therapy

Multiple Sclerosis Journal ◽

10.1177/1352458513481395 ◽

2013 ◽

Vol 19 (9) ◽

pp. 1230-1233 ◽

Cited By ~ 11

Author(s):

Akiko Yokoseki ◽

Etsuji Saji ◽

Musashi Arakawa ◽

Mariko Hokari ◽

Takanobu Ishiguro ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

T Cells ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Ccr7 Expression ◽

Blood Lymphocytes ◽

Sphingosine 1 Phosphate ◽

Secondary Lymphoid Organs

Fingolimod acts as a functional antagonist of the sphingosine-1-phosphate receptor, and it traps lymphocytes in secondary lymphoid organs and precludes their migration into the central nervous system. We report the case of a patient who suffered a relatively severe relapse of multiple sclerosis (MS) during the initial 3 months of fingolimod therapy, with retention of CCR7 expression on CD4+ T cells in the cerebrospinal fluid (CSF) despite decreased numbers of lymphocytes and decreased expression of CCR7 on CD4+ T cells in the blood. These data suggest that fingolimod may cause differential effects on the CSF and blood lymphocytes of patients with MS during the initial months of therapy.

Faculty Opinions recommendation of T cells become licensed in the lung to enter the central nervous system.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717953783.793460493 ◽

2012 ◽

Author(s):

William A Muller

Keyword(s):

Central Nervous System ◽

T Cells ◽

Nervous System ◽

Development of the Cerebrospinal Fluid in Early Stage after Hemorrhage in the Central Nervous System

Life ◽

10.3390/life11040300 ◽

2021 ◽

Vol 11 (4) ◽

pp. 300

Author(s):

Petr Kelbich ◽

Aleš Hejčl ◽

Jan Krejsek ◽

Tomáš Radovnický ◽

Inka Matuchová ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Early Stage ◽

Rank Test ◽

Signed Rank ◽

Signed Rank Test ◽

Poor Outcomes ◽

Molecular Patterns

Extravasation of blood in the central nervous system (CNS) represents a very strong damaged associated molecular patterns (DAMP) which is followed by rapid inflammation and can participate in worse outcome of patients. We analyzed cerebrospinal fluid (CSF) from 139 patients after the CNS hemorrhage. We compared 109 survivors (Glasgow Outcome Score (GOS) 5-3) and 30 patients with poor outcomes (GOS 2-1). Statistical evaluations were performed using the Wilcoxon signed-rank test and the Mann–Whitney U test. Almost the same numbers of erythrocytes in both subgroups appeared in days 0–3 (p = 0.927) and a significant increase in patients with GOS 2-1 in days 7–10 after the hemorrhage (p = 0.004) revealed persistence of extravascular blood in the CNS as an adverse factor. We assess 43.3% of patients with GOS 2-1 and only 27.5% of patients with GOS 5-3 with low values of the coefficient of energy balance (KEB < 15.0) in days 0–3 after the hemorrhage as a trend to immediate intensive inflammation in the CNS of patients with poor outcomes. We consider significantly higher concentration of total protein of patients with GOS 2-1 in days 0–3 after hemorrhage (p = 0.008) as the evidence of immediate simultaneously manifested intensive inflammation, swelling of the brain and elevation of intracranial pressure.