scholarly journals The T Cell Response to IL-10 Alters Cellular Dynamics and Paradoxically Promotes Central Nervous System Autoimmunity

2012 ◽  
Vol 189 (2) ◽  
pp. 669-678 ◽  
Author(s):  
Xin Liu ◽  
Rajshekhar Alli ◽  
Meredith Steeves ◽  
Phuong Nguyen ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cellular Dynamics

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 Generation of a Protective T-Cell Response Following Coronavirus Infection of the Central Nervous System Is Not Dependent on IL-12/23 Signaling

2008 ◽  
Vol 21 (2) ◽  
pp. 173-188 ◽  
Author(s):  
Katherine S. Held ◽  
William G. Glass ◽  
Yevgeniya I. Orlovsky ◽  
Kimberly A. Shamberger ◽  
Ted D. Petley ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
The Central Nervous System ◽  
Coronavirus Infection

scholarly journals Early T cell response in the central nervous system in canine distemper virus infection

1999 ◽  
Vol 97 (1) ◽  
pp. 45-56 ◽  
Author(s):  
A. Tipold ◽  
P. Moore ◽  
A. Zurbriggen ◽  
I. Burgener ◽  
G. Barben ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
Virus Infection ◽  
Cell Response ◽  
Canine Distemper Virus ◽  
T Cell Response ◽  
Canine Distemper ◽  
The Central Nervous System

scholarly journals Immune-Mediated Protection from Measles Virus-Induced Central Nervous System Disease Is Noncytolytic and Gamma Interferon Dependent

2002 ◽  
Vol 76 (9) ◽  
pp. 4497-4506 ◽  
Author(s):  
Catherine E. Patterson ◽  
Diane M. P. Lawrence ◽  
Lisa A. Echols ◽  
Glenn F. Rall
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
T Cell ◽  
Neuronal Death ◽  
Measles Virus ◽  
Critical Role ◽  
Gamma Interferon ◽  
T Cell Response ◽  
Ifn Γ

ABSTRACT Neurons of the mammalian central nervous system (CNS) are an essential and largely nonrenewable cell population. Thus, virus infections that result in neuronal depletion, either by virus-mediated cell death or by induction of the cytolytic immune response, could cause permanent neurological impairment of the host. In a transgenic mouse model of measles virus (MV) infection of neurons, we have previously shown that the host T-cell response was required for resolution of infection in susceptible adult mice. In this report, we show that this protective response did not result in neuronal death, even during the peak of T-cell infiltration into the brain parenchyma. When susceptible mice were intercrossed with specific immune knockout mice, a critical role for gamma interferon (IFN-γ) was identified in protection against MV infection and CNS disease. Moreover, the addition of previously activated splenocytes or recombinant murine IFN-γ to MV-infected primary neurons resulted in the inhibition of viral replication in the absence of neuronal death. Together, these data support the hypothesis that the host immune response can promote viral clearance without concomitant neuronal loss, a process that appears to be mediated by cytokines.

scholarly journals Dopaminergic stimulation leads B-cell infiltration into the central nervous system upon autoimmunity

2020 ◽  
Author(s):  
Carolina Prado ◽  
Francisco Osorio-Barrios ◽  
Alexandra Espinoza ◽  
Juan J Saez ◽  
María I Yuseff ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
B Cells ◽  
Animal Models ◽  
B Cell ◽  
T Cell Response ◽  
Autoimmune Response ◽  
Cns Autoimmunity ◽  
Anti Inflammatory

Abstract Background: Recent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation of adaptive and innate immune cells plays an important role in the physiopathology of inflammatory disorders. Multiple sclerosis (MS) is an inflammatory disease involving a CD4+ T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models has suggested that B-cells play a fundamental role as antigen-presenting cells (APC) re-stimulating CD4+ T-cells in the CNS as well as regulating T-cell response by mean of inflammatory or anti-inflammatory cytokines. Here we addressed the role of the dopamine receptor D3 (DRD3), which display the highest affinity for dopamine, in B-cells in animal models of MS.Methods: Mice harbouring Drd3-deficient or Drd3-suficient B-cells were generated by bone marrow transplantation into recipient mice devoid of B-cells. In these mice we compare the development of experimental autoimmune encephalomyelitis (EAE) induced by immunization with a myelin oligodendrocyte glycoprotein (MOG)-derived peptide (pMOG), a model that leads to CNS-autoimmunity irrespective of the APC function of B-cells, or by immunization with full-length human MOG protein (huMOG), a model in which antigen-specific activated B-cells display a fundamental APCs function in the CNS. Results: Our data shows that, by promoting the expression of the chemokine receptor CXCR3 in autoreactive B-cells, DRD3-stimulation favours the CNS-tropism in a subset of B-cells that act as APC in the CNS, which is fundamental for disease development. Furthermore, we found that DRD3- stimulation induced the expression of the CNS-homing molecule CD49d in a B-cell subset with anti-inflammatory features, thus attenuating EAE manifestation in a CNS-autoimmunity model independent of the APC function of B-cells.Conclusion: Our findings demonstrate that DRD3-stimulation in B-cells exerts a dual role in CNS-autoimmunity, favouring CNS-tropism of pro-inflammatory B-cells with APC function, and also promoting CNS-homing of B-cells with anti-inflammatory features. Thus, these results show DRD3-stimulation in B-cells as a key regulator of CNS-autoimmunity.

scholarly journals Dopaminergic Stimulation Leads B-cell Infiltration into the Central Nervous System upon Autoimmunity

2021 ◽  
Author(s):  
Carolina Prado ◽  
Francisco Osorio-Barrios ◽  
Alexandra Espinoza ◽  
Juan J Saez ◽  
María I Yuseff ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
B Cells ◽  
Animal Models ◽  
B Cell ◽  
T Cell Response ◽  
Autoimmune Response ◽  
Cns Autoimmunity ◽  
Anti Inflammatory

Abstract Background. Recent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation of adaptive and innate immune cells plays an important role in the physiopathology of inflammatory disorders. Multiple sclerosis (MS) is an inflammatory disease involving a CD4+ T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models has suggested that B-cells play a fundamental role as antigen-presenting cells (APC) re-stimulating CD4+ T-cells in the CNS as well as regulating T-cell response by mean of inflammatory or anti-inflammatory cytokines. Here we addressed the role of the dopamine receptor D3 (DRD3), which display the highest affinity for dopamine, in B-cells in animal models of MS. Methods. Mice harbouring Drd3-deficient or Drd3-suficient B-cells were generated by bone marrow transplantation into recipient mice devoid of B-cells. In these mice we compare the development of experimental autoimmune encephalomyelitis (EAE) induced by immunization with a myelin oligodendrocyte glycoprotein (MOG)-derived peptide (pMOG), a model that leads to CNS-autoimmunity irrespective of the APC function of B-cells, or by immunization with full-length human MOG protein (huMOG), a model in which antigen-specific activated B-cells display a fundamental APCs function in the CNS.Results. Our data shows that, by promoting the expression of the chemokine receptor CXCR3 in autoreactive B-cells, DRD3-stimulation favours the CNS-tropism in a subset of B-cells that act as APC in the CNS, which is fundamental for disease development. Furthermore, we found that DRD3- stimulation induced the expression of the CNS-homing molecule CD49d in a B-cell subset with anti-inflammatory features, thus attenuating EAE manifestation in a CNS-autoimmunity model independent of the APC function of B-cells.Conclusions. Our findings demonstrate that DRD3-stimulation in B-cells exerts a dual role in CNS-autoimmunity, favouring CNS-tropism of pro-inflammatory B-cells with APC function, and also promoting CNS-homing of B-cells with anti-inflammatory features. Thus, these results show DRD3-signalling in B-cells as a key regulator of CNS-autoimmunity.

scholarly journals Dopaminergic stimulation leads B-cell infiltration into the central nervous system upon autoimmunity

2021 ◽  
Author(s):  
Carolina Prado ◽  
Francisco Osorio-Barrios ◽  
Alexandra Espinoza ◽  
Juan J Saez ◽  
María I Yuseff ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Response ◽  
Autoimmune Response ◽  
Cns Autoimmunity ◽  
Anti Inflammatory

Abstract Multiple sclerosis (MS) involves a CD4+ T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Previous evidence has suggested that B-cells play a fundamental role as antigen-presenting cells (APC) in mouse models of MS re-stimulating CD4+ T-cells in the CNS as well as regulating the T-cell response by mean of inflammatory or anti-inflammatory cytokines. Despite an important dopaminergic regulation of T-cells has been previously described in MS, the effects of dopaminergic signalling in B-cells in this pathology remains unexplored. Here we addressed the role of the dopamine receptor D3 (DRD3), which display the highest affinity for dopamine, in B-cells in animal models of MS. Experimental autoimmune encephalomyelitis (EAE) was induced in mice harbouring Drd3-deficient or Drd3-suficient B-cells. Our data shows that, by promoting the expression of the chemokine receptor CXCR3 in autoreactive B-cells, DRD3-stimulation favours the CNS-tropism in a subset of B-cells that act as APC in the CNS, which is fundamental for disease development. Furthermore, we found that DRD3-stimulation induced the expression of the CNS-homing molecule CD49d in a B-cell subset with anti-inflammatory features, thus attenuating EAE manifestation in a CNS-autoimmunity model independent of the APC function of B-cells. Our findings demonstrate that DRD3-stimulation in B-cells exerts a dual role in CNS-autoimmunity, favouring CNS-tropism of pro-inflammatory B-cells with APC function, and also promoting CNS-homing of B-cells with anti-inflammatory features. Thus, these results show DRD3-stimulation in B-cells as a key regulator of CNS-autoimmunity.

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