scholarly journals CC Chemokines Mediate Leukocyte Trafficking into the Central Nervous System during Murine Neurocysticercosis: Role of γδ T Cells in Amplification of the Host Immune Response

2003 ◽  
Vol 71 (5) ◽  
pp. 2634-2642 ◽  
Author(s):  
Astrid E. Cardona ◽  
Paula A. Gonzalez ◽  
Judy M. Teale
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Γδ T Cells ◽  
Host Immune Response ◽  
Leukocyte Trafficking ◽  
Cellular Infiltration ◽  
The Brain

ABSTRACT According to a previous report, the degree of the host immune response highly correlates with severity of the disease in the murine model for neurocysticercosis. In wild-type mice, Mesocestoides corti infection induced a rapid and extensive accumulation of γδ T cells and macrophages in the brain. NK cells, dendritic cells, αβ T cells, and B cells were also recruited to the brain but at lower levels. In contrast, γδ T-cell-deficient mice exhibited decreased cellular infiltration and reduced central nervous system (CNS) pathology. To understand the mechanisms of leukocyte recruitment into the CNS, chemokine expression was analyzed in infected brains in the present study. MCP-1 (CCL2), MIP-1α (CCL3), and MIP-1β (CCL4) were up-regulated within 2 days after M. corti infection. Protein expression of RANTES (CCL5), eotaxin (CCL11), and MIP-2 was detected later, at 1 week postinfection. Correlating with the decreased cellular infiltration, delta chain T-cell receptor-deficient (TCRδ−/−) mice exhibited substantially reduced levels of most of the chemokines analyzed (with the exception of eotaxin). The results suggest that γδ T cells play an important role in the CNS immune response by producing chemokines such as MCP-1 and MIP-1α, enhancing leukocyte trafficking into the brain during murine neurocysticercosis.

scholarly journals Developmental Dysfunction of the Central Nervous System Lymphatics Modulates the Adaptive Neuro-Immune Response in the Perilesional Cortex in a Mouse Model of Traumatic Brain Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Sara Wojciechowski ◽  
Anaïs Virenque ◽  
Maria Vihma ◽  
Barbara Galbardi ◽  
Erin Jane Rooney ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Immune Response ◽  
T Cells ◽  
Nervous System ◽  
Brain Injury ◽  
T Cell ◽  
Lesion Volume ◽  
The Central Nervous System ◽  
The Brain

RationaleThe recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous system. The role of mLVs in modulating the neuro-immune response following a traumatic brain injury (TBI), however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after TBI, suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of T cell response in the brain after TBI.MethodsTBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI.ResultsIn both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44hiCD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, suggesting that mLVs could be involved in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate to alterations in peripheral circulating T cells, as assessed one month after injury.ConclusionsOur results are consistent with the hypothesis that mLVs are involved in the neuro-immune response after TBI. We also defined the resident memory CD8+ T cells as one of the main population activated within the brain after a traumatic injury.

scholarly journals Priming of CD8+ T Cells during Central Nervous System Infection with a Murine Coronavirus Is Strain Dependent

2008 ◽  
Vol 82 (13) ◽  
pp. 6150-6160 ◽  
Author(s):  
Katherine C. MacNamara ◽  
Susan J. Bender ◽  
Ming Ming Chua ◽  
Richard Watson ◽  
Susan R. Weiss
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cns Infection ◽  
Cervical Lymph Nodes ◽  
T Cell Priming ◽  
The Brain

ABSTRACT Virus-specific CD8+ T cells are critical for protection against neurotropic coronaviruses; however, central nervous system (CNS) infection with the recombinant JHM (RJHM) strain of mouse hepatitis virus (MHV) elicits a weak CD8+ T-cell response in the brain and causes lethal encephalomyelitis. An adoptive transfer model was used to elucidate the kinetics of CD8+ T-cell priming during CNS infection with RJHM as well as with two MHV strains that induce a robust CD8+ T-cell response (RA59 and SJHM/RA59, a recombinant A59 virus expressing the JHM spike). While RA59 and SJHM/RA59 infections resulted in CD8+ T-cell priming within the first 2 days postinfection, RJHM infection did not lead to proliferation of naïve CD8+ T cells. While all three viruses replicated efficiently in the brain, only RA59 and SJHM/RA59 replicated to appreciable levels in the cervical lymph nodes (CLN), the site of T-cell priming during acute CNS infection. RJHM was unable to suppress the CD8+ T-cell response elicited by RA59 in mice simultaneously infected with both strains, suggesting that RJHM does not cause generalized immunosuppression. RJHM was also unable to elicit a secondary CD8+ T-cell response in the brain following peripheral immunization against a viral epitope. Notably, the weak CD8+ T-cell response elicited by RJHM was unique to CNS infection, since peripheral inoculation induced a robust CD8+ T-cell response in the spleen. These findings suggest that the failure of RJHM to prime a robust CD8+ T-cell response during CNS infection is likely due to its failure to replicate in the CLN.

scholarly journals The role of unconventional T cells in COVID-19

2021 ◽  
Author(s):  
Kristen Orumaa ◽  
Margaret R. Dunne
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Treatment Strategies ◽  
Γδ T Cells ◽  
Protective Role ◽  
T Cell Subsets ◽  
Viral Immunity ◽  
Mait Cells

AbstractCOVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first documented in late 2019, but within months, a worldwide pandemic was declared due to the easily transmissible nature of the virus. Research to date on the immune response to SARS-CoV-2 has focused largely on conventional B and T lymphocytes. This review examines the emerging role of unconventional T cell subsets, including γδ T cells, invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells in human SARS-CoV-2 infection.Some of these T cell subsets have been shown to play protective roles in anti-viral immunity by suppressing viral replication and opsonising virions of SARS-CoV. Here, we explore whether unconventional T cells play a protective role in SARS-CoV-2 infection as well. Unconventional T cells are already under investigation as cell-based immunotherapies for cancer. We discuss the potential use of these cells as therapeutic agents in the COVID-19 setting. Due to the rapidly evolving situation presented by COVID-19, there is an urgent need to understand the pathogenesis of this disease and the mechanisms underlying its immune response. Through this, we may be able to better help those with severe cases and lower the mortality rate by devising more effective vaccines and novel treatment strategies.

Electrical Properties and Anion Permeability of Doubly Rectifying Junctions in the Leech Central Nervous System

1988 ◽  
Vol 137 (1) ◽  
pp. 1-11
Author(s):  
Susan E. Acklin
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Action Potentials ◽  
Sodium Pump ◽  
Current Flow ◽  
Cell Movement ◽  
Voltage Dependent ◽  
Electrical Connections

A study has been made of the electrical connections between touch sensory (T) neurones in the leech central nervous system (CNS) which display remarkable double rectification: depolarization spreads in both directions although hyperpolarization spreads poorly. Tests were made to determine whether this double rectification was a property of the junctions themselves or whether it resulted from changes in the length constants of processes intervening between the cell body and the junctions. Following trains of action potentials, T cells and their fine processes within the neuropile became hyperpolarized through the activity of an electrogenie sodium pump. When any T cell was hyperpolarized by 25 mV by repetitive stimulation, hyperpolarization failed to spread to the T cells to which it was electrically coupled. Further evidence for double rectification of junctions linking T cells was provided by experiments in which Cl− was injected electrophoretically. Cl− injection into one T cell caused inhibitory potentials recorded in it to become reversed. After a delay, Cl− spread to reverse IPSPs in the coupled T cell. Movement of Cl−, like current flow, was dependent on membrane potential. When the T cell into which Cl− was injected was kept hyperpolarized, Cl− failed to move into the adjacent T cell. Upon release of the hyperpolarization in the injected T cell, Cl− moved and reversed IPSPs in the coupled T cell. Together these results indicate that the gating properties of channels linking T cells are voltage-dependent, such that depolarization of either cell allows channels to open whereas hyperpolarization causes them to close.

scholarly journals Identification of leptospiral protein antigens recognized by WC1+ γδ T cell subsets as target for development of recombinant vaccines

2021 ◽  
Author(s):  
Aline Teixeira ◽  
Alexandria Gillespie ◽  
Alehegne Yirsaw ◽  
Emily Britton ◽  
Janice Telfer ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Outer Membrane Proteins ◽  
Γδ T Cells ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Economic Losses ◽  
Γδ T Cell ◽  
Protein Antigens

Pathogenic Leptospira species cause leptospirosis, a neglected zoonotic disease recognized as a global public health problem. It is also the cause of the most common cattle infection that results in major economic losses due to reproductive problems. γδ T cells play a role in the protective immune response in livestock species against Leptospira while human γδ T cells also respond to Leptospira. Thus, activation of γδ T cells has emerged as a potential component for optimization of vaccine strategies. Bovine γδ T cells proliferate and produce IFN-γ in response to vaccination with inactivated leptospires and this response is mediated by a specific subpopulation of the WC1-bearing γδ T cells. WC1 molecules are members of the group B scavenger receptor cysteine rich (SRCR) superfamily and are composed of multiple SRCR domains, of which particular extracellular domains act as ligands for Leptospira. Since WC1 molecules function as both pattern recognition receptors and γδ TCR coreceptors, the WC1 system has been proposed as a novel target to engage γδ T cells. Here, we demonstrate the involvement of leptospiral protein antigens in the activation of WC1+ γδ T cells and identified two leptospiral outer membrane proteins able to interact directly with them. Interestingly, we show that the protein-specific γδ T cell response is composed of WC1.1+ and WC1.2+ subsets, although a greater number of WC1.1+ γδ T cells respond. Identification of protein antigens will enhance our understanding of the role γδ T cells play in the leptospiral immune response and in recombinant vaccine development.

Characterization of a Unique γδ T-Cell Subset as a Specific Marker of Cytomegalovirus Infection Severity

2020 ◽  
Author(s):  
Hannah Kaminski ◽  
Coline Ménard ◽  
Bouchra El Hayani ◽  
And-Nan Adjibabi ◽  
Gabriel Marsères ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Subset ◽  
Γδ T Cells ◽  
Specific Marker ◽  
Dependent Manner ◽  
Γδ T Cell ◽  
T Cell Subset ◽  
Cmv Disease

Abstract Cytomegalovirus (CMV) is a major infectious cause of death and disease after transplantation. We have previously demonstrated that the tissue-associated adaptive Vδ2neg γδ T cells are key effectors responding to CMV and associated with recovery, contrasting with their innatelike circulating counterparts, the Vγ9posVδ2pos T cells that respond to phosphoantigens but not to CMV. A third Vγ9negVδ2pos subgroup with adaptive functions has been described in adults. In the current study, we demonstrate that these Vγ9negVδ2pos T cells are also components of the CMV immune response while presenting with distinct characteristics from Vδ2neg γδ T cells. In a cohort of kidney transplant recipients, CMV seropositivity was the unique clinical parameter associated with Vγ9negVδ2pos T-cell expansion and differentiation. Extensive phenotyping demonstrated their substantial cytotoxic potential and activation during acute CMV primary infection or reinfection. In vitro, Vγ9negVδ2pos T cells responded specifically to CMV-infected cells in a T-cell receptor–dependent manner and through strong interferon γ production. Finally, Vγ9negVδ2pos T cells were the only γδ T-cell subset in which expansion was tightly correlated with the severity of CMV disease. To conclude, our results identify a new player in the immune response against CMV and open interesting clinical perspectives for using Vγ9negVδ2pos T cells as an immune marker for CMV disease severity in immunocompromised patients.

Immune Response of Human Propagated γδ-T-Cells to Neuroblastoma Recommend the Vδ1+ Subset for γδ-T-cell–based Immunotherapy

2008 ◽  
Vol 31 (9) ◽  
pp. 896-905 ◽  
Author(s):  
Karin Schilbach ◽  
Klaus Frommer ◽  
Sybille Meier ◽  
Rupert Handgretinger ◽  
Matthias Eyrich
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Γδ T Cells ◽  
Γδ T Cell

scholarly journals Circulating γδ T Cells in Response to Salmonellaenterica Serovar Enteritidis Exposure in Chickens

2006 ◽  
Vol 74 (7) ◽  
pp. 3967-3978 ◽  
Author(s):  
Angela Berndt ◽  
Jana Pieper ◽  
Ulrich Methner
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Type Strain ◽  
Wild Type Strain ◽  
Γδ T Cells ◽  
Immunohistochemical Analysis ◽  
Wild Type ◽  
Γδt Cells

ABSTRACT γδT cells are considered crucial to the outcome of various infectious diseases. The present study was undertaken to characterizeγδ (T-cell receptor 1+ [TCR1+]) T cells phenotypically and functionally in avian immune response. Day-old chicks were orally immunized with Salmonella enterica serovar Enteritidis live vaccine or S. enterica serovar Enteritidis wild-type strain and infected using the S. enterica serovar Enteritidis wild-type strain on day 44 of life. Between days 3 and 71, peripheral blood was examined flow cytometrically for the occurrence of γδ T-cell subpopulations differentiated by the expression of T-cell antigens. Three different TCR1+ cell populations were found to display considerable variation regarding CD8α antigen expression: (i) CD8α+high TCR1+ cells, (ii) CD8α+dim TCR1+ cells, and (iii) CD8α− TCR1+ cells. While most of the CD8α+high TCR1+ cells expressed the CD8αβ heterodimeric antigen, the majority of the CD8α+dim TCR1+ cells were found to express the CD8αα homodimeric form. After immunization, a significant increase of CD8αα+high γδ T cells was observed within the CD8α+high TCR1+ cell population. Quantitative reverse transcription-PCR revealed reduced interleukin-7 receptor α (IL-7Rα) and Bcl-x expression and elevated IL-2Rα mRNA expression of the CD8αα+highγδ T cells. Immunohistochemical analysis demonstrated a significant increase of CD8α+ and TCR1+ cells in the cecum and spleen and a decreased percentage of CD8β+ T cells in the spleen after Salmonella immunization. After infection of immunized animals, immune reactions were restricted to intestinal tissue. The study showed that Salmonella immunization of very young chicks is accompanied by an increase of CD8αα+high γδ T cells in peripheral blood, which are probably activated, and thus represent an important factor for the development of a protective immune response to Salmonella organisms in chickens.

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