scholarly journals The functional avidity of virus-specific CD8+ T?cells is down-modulated in Borna disease virus-induced immunopathology of the central nervous system

2005 ◽  
Vol 35 (2) ◽  
pp. 487-497 ◽  
Author(s):  
Karin?R. Engelhardt ◽  
Kirsten Richter ◽  
Karen Baur ◽  
Peter Staeheli ◽  
J�rgen Hausmann
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Disease Virus ◽  
Cd8 T Cells ◽  
Functional Avidity ◽  
Borna Disease Virus ◽  
The Central Nervous System ◽  
Borna Disease

scholarly journals Borna Disease Virus Accelerates Inflammation and Disease Associated with Transgenic Expression of Interleukin-12 in the Central Nervous System

2002 ◽  
Vol 76 (23) ◽  
pp. 12223-12232 ◽  
Author(s):  
Susanna Freude ◽  
Jürgen Hausmann ◽  
Markus Hofer ◽  
Ngan Pham-Mitchell ◽  
Iain L. Campbell ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Disease Virus ◽  
Biologically Active ◽  
Interleukin 12 ◽  
Wild Type ◽  
Borna Disease Virus ◽  
The Central Nervous System ◽  
Borna Disease

ABSTRACT Targeted expression of biologically active interleukin-12 (IL-12) in astrocytes of the central nervous system (CNS) results in spontaneous neuroimmunological disease of aged mice. Borna disease virus (BDV) can readily multiply in the mouse CNS but does not trigger disease in most strains. Here we show that a large percentage of IL-12 transgenic mice developed severe ataxia within 5 to 10 weeks after infection with BDV. By contrast, no disease developed in mock-infected IL-12 transgenic and wild-type mice until 4 months of age. Neurological symptoms were rare in infected wild-type animals, and if they occurred, these were milder and appeared later. Histological analyses showed that the cerebellum of infected IL-12 transgenic mice, which is the brain region with strongest transgene expression, contained large numbers of CD4+ and CD8+ T cells as well as lower numbers of B cells, whereas other parts of the CNS showed only mild infiltration by lymphocytes. The cerebellum of diseased mice further showed severe astrogliosis, calcifications and signs of neurodegeneration. BDV antigen and nucleic acids were present in lower amounts in the inflamed cerebellum of infected transgenic mice than in the noninflamed cerebellum of infected wild-type littermates, suggesting that IL-12 or IL-12-induced cytokines exhibited antiviral activity. We propose that BDV infection accelerates the frequency by which immune cells such as lymphocytes and NK cells enter the CNS and then respond to IL-12 present in the local milieu causing disease. Our results illustrate that infection of the CNS with a virus that is benign in certain hosts can be harmful in such normally disease-resistant hosts if the tissue is unfavorably preconditioned by proinflammatory cytokines.

scholarly journals Intrinsic responses to Borna disease virus infection of the central nervous system

1996 ◽  
Vol 93 (23) ◽  
pp. 13345-13350 ◽  
Author(s):  
K. Morimoto ◽  
D. C. Hooper ◽  
A. Bornhorst ◽  
S. Corisdeo ◽  
M. Bette ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Virus Infection ◽  
Disease Virus ◽  
Borna Disease Virus ◽  
The Central Nervous System ◽  
Borna Disease

scholarly journals CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

2005 ◽  
Vol 79 (21) ◽  
pp. 13509-13518 ◽  
Author(s):  
Jürgen Hausmann ◽  
Axel Pagenstecher ◽  
Karen Baur ◽  
Kirsten Richter ◽  
Hanns-Joachim Rziha ◽  
...  
Keyword(s):  
T Cells ◽  
Disease Virus ◽  
Cd8 T Cells ◽  
Gamma Interferon ◽  
Wild Type ◽  
Borna Disease Virus ◽  
Ifn Γ ◽  
The Brain ◽  
Deficient Mice ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain MRL. Disease does not result from the virus-induced destruction of infected neurons. Rather, it is mediated by H-2 k -restricted antiviral CD8 T cells that recognize a peptide derived from the BDV nucleoprotein N. Persistent BDV infection in mice is not spontaneously cleared. We report here that N-specific vaccination can protect wild-type MRL mice but not mutant MRL mice lacking gamma interferon (IFN-γ) from persistent infection with BDV. Furthermore, we observed a significant degree of resistance of old MRL mice to persistent BDV infection that depended on the presence of CD8 T cells. We found that virus initially infected hippocampal neurons around 2 weeks after intracerebral infection but was eventually cleared in most wild-type MRL mice. Unexpectedly, young as well as old IFN-γ-deficient MRL mice were completely susceptible to infection with BDV. Moreover, neurons in the CA1 region of the hippocampus were severely damaged in most diseased IFN-γ-deficient mice but not in wild-type mice. Furthermore, large numbers of eosinophils were present in the inflamed brains of IFN-γ-deficient mice but not in those of wild-type mice, presumably because of increased intracerebral synthesis of interleukin-13 and the chemokines CCL1 and CCL11, which can attract eosinophils. These results demonstrate that IFN-γ plays a central role in host resistance against infection of the central nervous system with BDV and in clearance of BDV from neurons. They further indicate that IFN-γ may function as a neuroprotective factor that can limit the loss of neurons in the course of antiviral immune responses in the brain.

scholarly journals Immunization with dendritic cells can break immunological ignorance toward a persisting virus in the central nervous system and induce partial protection against intracerebral viral challenge

2004 ◽  
Vol 85 (8) ◽  
pp. 2379-2387 ◽  
Author(s):  
Ulrike Fassnacht ◽  
Andreas Ackermann ◽  
Peter Staeheli ◽  
Jürgen Hausmann
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Recombinant Vaccinia Virus ◽  
Immune Memory ◽  
Cervical Lymph Nodes ◽  
The Central Nervous System

Dendritic cells (DCs) have been used successfully to induce CD8 T cells that control virus infections and growth of tumours. The efficacy of DC-mediated immunization for the control of neurotropic Borna disease virus (BDV) in mice was evaluated. Certain strains of mice only rarely develop spontaneous neurological disease, despite massive BDV replication in the brain. Resistance to disease is due to immunological ignorance toward BDV antigen in the central nervous system. Ignorance in mice can be broken by immunization with DCs coated with TELEISSI, a peptide derived from the N protein of BDV, which represents the immunodominant cytotoxic T lymphocyte epitope in H-2k mice. Immunization with TELEISSI-coated DCs further induced solid protective immunity against intravenous challenge with a recombinant vaccinia virus expressing BDV-N. Interestingly, however, this immunization scheme induced only moderate protection against intracerebral challenge with BDV, suggesting that immune memory raised against a shared antigen may be sufficient to control a peripherally replicating virus, but not a highly neurotropic virus that is able to avoid activation of T cells. This difference might be due to the lack of BDV-specific CD4 T cells and/or inefficient reactivation of DC-primed, BDV-specific CD8 T cells by the locally restricted BDV infection. Thus, a successful vaccine against persistent viruses with strong neurotropism should probably induce antiviral CD8 (as well as CD4) T-cell responses and should favour the accumulation of virus-specific memory T cells in cervical lymph nodes.

scholarly journals Migration of CD8+T Cells into the Central Nervous System Gives Rise to Highly Potent Anti-HIV CD4dimCD8brightT Cells in a Wnt Signaling–Dependent Manner

2015 ◽  
Vol 196 (1) ◽  
pp. 317-327 ◽  
Author(s):  
Maureen H. Richards ◽  
Srinivas D. Narasipura ◽  
Melanie S. Seaton ◽  
Victoria Lutgen ◽  
Lena Al-Harthi
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Wnt Signaling ◽  
Cd8 T Cells ◽  
Dependent Manner ◽  
The Central Nervous System ◽  
Anti Hiv
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