scholarly journals Immune Autoregulatory CD8 T Cells Require IFN-γ Responsiveness to Optimally Suppress Central Nervous System Autoimmunity

2020 ◽  
Vol 205 (2) ◽  
pp. 359-368
Author(s):  
Alexander W. Boyden ◽  
Ashley A. Brate ◽  
Laura M. Stephens ◽  
Nitin J. Karandikar
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd8 T Cells ◽  
Ifn Γ

scholarly journals Perforin and Gamma Interferon-Mediated Control of Coronavirus Central Nervous System Infection by CD8 T Cells in the Absence of CD4 T Cells

2004 ◽  
Vol 78 (4) ◽  
pp. 1739-1750 ◽  
Author(s):  
Cornelia C. Bergmann ◽  
Beatriz Parra ◽  
David R. Hinton ◽  
Chandran Ramakrishna ◽  
Konechi C. Dowdell ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Virus Replication ◽  
Cell Types ◽  
Cytolytic Activity ◽  
Gamma Interferon ◽  
Effective Control ◽  
Viral Control ◽  
Ifn Γ

ABSTRACT Infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus produces acute and chronic demyelination. The contributions of perforin-mediated cytolysis and gamma interferon (IFN-γ) secretion by CD8+ T cells to the control of infection and the induction of demyelination were examined by adoptive transfer into infected SCID recipients. Untreated SCID mice exhibited uncontrolled virus replication in all CNS cell types but had little or no demyelination. Memory CD8+ T cells from syngeneic wild-type (wt), perforin-deficient, or IFN-γ-deficient (GKO) donors all trafficked into the infected CNS in the absence of CD4+ T cells and localized to similar areas. Although CD8+ T cells from all three donors suppressed virus replication in the CNS, GKO CD8+ T cells expressed the least antiviral activity. A distinct viral antigen distribution in specific CNS cell types revealed different mechanisms of viral control. While wt CD8+ T cells inhibited virus replication in all CNS cell types, cytolytic activity in the absence of IFN-γ suppressed the infection of astrocytes, but not oligodendroglia. In contrast, cells that secreted IFN-γ but lacked cytolytic activity inhibited replication in oligodendroglia, but not astrocytes. Demyelination was most severe following viral control by wt CD8+ T cells but was independent of macrophage infiltration. These data demonstrate the effective control of virus replication by CD8+ T cells in the absence of CD4+ T cells and support the necessity for the expression of distinct effector mechanisms in the control of viral replication in distinct CNS glial cell types.

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 The Majority of Infiltrating CD8+ T Cells in the Central Nervous System of Susceptible SJL/J Mice Infected with Theiler's Virus Are Virus Specific and Fully Functional

2002 ◽  
Vol 76 (13) ◽  
pp. 6577-6585 ◽  
Author(s):  
Bong-Su Kang ◽  
Michael A. Lyman ◽  
Byung S. Kim
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Demyelinating Disease ◽  
Class I ◽  
Theiler's Virus ◽  
Ctl Response ◽  
The Central Nervous System ◽  
Ifn Γ

ABSTRACT Theiler's virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains, such as SJL/J, and serves as a relevant infectious model for human multiple sclerosis. It has been previously suggested that susceptible SJL/J mice do not mount an efficient cytotoxic T-lymphocyte (CTL) response to the virus. In addition, genetic studies have shown that resistance to Theiler's virus-induced demyelinating disease is linked to the H-2D major histocompatibility complex class I locus, suggesting that a compromised CTL response may contribute to the susceptibility of SJL/J mice. Here we show that SJL/J mice do, in fact, generate a CD8+ T-cell response in the CNS that is directed against one dominant (VP3159-166) and two subdominant (VP111-20 and VP3173-181) capsid protein epitopes. These virus-specific CD8+ T cells produce gamma interferon (IFN-γ) and lyse target cells in the presence of the epitope peptides, indicating that these CNS-infiltrating CD8+ T cells are fully functional effector cells. Intracellular IFN-γ staining analysis indicates that greater than 50% of CNS-infiltrating CD8+ T cells are specific for these viral epitopes at 7 days postinfection. Therefore, the susceptibility of SJL/J mice is not due to the lack of an early functional Theiler's murine encephalomyelitis virus-specific CTL response. Interestingly, T-cell responses to all three epitopes are restricted by the H-2Ks molecule, and this skewed class I restriction may be associated with susceptibility to demyelinating disease.

scholarly journals Critical Roles of NK and CD8+T Cells in Central Nervous System Listeriosis

2009 ◽  
Vol 182 (10) ◽  
pp. 6360-6368 ◽  
Author(s):  
Toshiyuki Hayashi ◽  
Shigenori Nagai ◽  
Hideki Fujii ◽  
Yukiko Baba ◽  
Eiji Ikeda ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd8 T Cells

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

2000 ◽  
Vol 165 (6) ◽  
pp. 3099-3104 ◽  
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 ◽  
The Central Nervous System ◽  
Ifn Γ

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

scholarly journals Protective Immunosurveillance of the Central Nervous System by Listeria-Specific CD4 and CD8 T Cells in Systemic Listeriosis in the Absence of Intracerebral Listeria

2002 ◽  
Vol 169 (4) ◽  
pp. 2010-2019 ◽  
Author(s):  
Lai-Yu Kwok ◽  
Hrvoje Miletic ◽  
Sonja Lütjen ◽  
Sabine Soltek ◽  
Martina Deckert ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd8 T Cells ◽  
The Central Nervous System

scholarly journals Migration of encephalitogenic CD8 T cells into the central nervous system is dependent on the α4β1-integrin

2015 ◽  
Vol 45 (12) ◽  
pp. 3302-3312 ◽  
Author(s):  
Guillaume Martin-Blondel ◽  
Béatrice Pignolet ◽  
Silvia Tietz ◽  
Lidia Yshii ◽  
Christina Gebauer ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd8 T Cells ◽  
The Central Nervous System

scholarly journals CD4 T Cells Contribute to Virus Control and Pathology following Central Nervous System Infection with Neurotropic Mouse Hepatitis Virus

2007 ◽  
Vol 82 (5) ◽  
pp. 2130-2139 ◽  
Author(s):  
Stephen A. Stohlman ◽  
David R. Hinton ◽  
Beatriz Parra ◽  
Roscoe Atkinson ◽  
Cornelia C. Bergmann
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Virus Replication ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Wild Type ◽  
Virus Control ◽  
Ifn Γ

ABSTRACT Replication of the neurotropic mouse hepatitis virus strain JHM (JHMV) is controlled primarily by CD8+ T-cell effectors utilizing gamma interferon (IFN-γ) and perforin-mediated cytotoxicity. CD4+ T cells provide an auxiliary function(s) for CD8+ T-cell survival; however, their direct contribution to control of virus replication and pathology is unclear. To examine a direct role of CD4+ T cells in viral clearance and pathology, pathogenesis was compared in mice deficient in both perforin and IFN-γ that were selectively reconstituted for these functions via transfer of virus-specific memory CD4+ T cells. CD4+ T cells from immunized wild-type, perforin-deficient, and IFN-γ-deficient donors all initially reduced virus replication. However, prolonged viral control by IFN-γ-competent donors suggested that IFN-γ is important for sustained virus control. Local release of IFN-γ was evident by up-regulation of class II molecules on microglia in recipients of IFN-γ producing CD4+ T cells. CD4+ T-cell-mediated antiviral activity correlated with diminished clinical symptoms, pathology, and demyelination. Both wild-type donor CD90.1 and recipient CD90.2 CD4+ T cells trafficked into the central nervous system (CNS) parenchyma and localized to infected white matter, correlating with decreased numbers of virus-infected oligodendrocytes in the CNS. These data support a direct, if limited, antiviral role for CD4+ T cells early during acute JHMV encephalomyelitis. Although the antiviral effector mechanism is initially independent of IFN-γ secretion, sustained control of CNS virus replication by CD4+ T cells requires IFN-γ.

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