scholarly journals High-Magnitude, Virus-Specific CD4 T-Cell Response in the Central Nervous System of Coronavirus-Infected Mice

2001 ◽  
Vol 75 (6) ◽  
pp. 3043-3047 ◽  
Author(s):  
Jodie S. Haring ◽  
Lecia L. Pewe ◽  
Stanley Perlman
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd4 T Cells ◽  
Hepatitis Virus ◽  
T Cell Response ◽  
Acute Encephalitis ◽  
High Magnitude ◽  
The Central Nervous System ◽  
Ifn Γ

ABSTRACT The neurotropic JHM strain of mouse hepatitis virus (MHV) causes acute encephalitis and chronic demyelinating encephalomyelitis in rodents. Previous results indicated that CD8 T cells infiltrating the central nervous system (CNS) were largely antigen specific in both diseases. Herein we show that by 7 days postinoculation, nearly 30% of the CD4 T cells in the acutely infected CNS were MHV specific by using intracellular gamma interferon (IFN-γ) staining assays. In mice with chronic demyelination, 10 to 15% of the CD4 T cells secreted IFN-γ in response to MHV-specific peptides. Thus, these results show that infection of the CNS is characterized by a large influx of CD4 T cells specific for MHV and that these cells remain functional, as measured by cytokine secretion, in mice with chronic demyelination.

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 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 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.

scholarly journals Kinetics of Virus-Specific CD8+-T-Cell Expansion and Trafficking following Central Nervous System Infection

2003 ◽  
Vol 77 (4) ◽  
pp. 2775-2778 ◽  
Author(s):  
Norman W. Marten ◽  
Stephen A. Stohlman ◽  
Jiehao Zhou ◽  
Cornelia C. Bergmann
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Hepatitis Virus ◽  
Acute Infection ◽  
Central Nervous System Infection ◽  
Cervical Lymph Nodes ◽  
Cognate Antigen ◽  
The Central Nervous System

ABSTRACT CD8+ T cells control acute infection of the central nervous system (CNS) by neurotropic mouse hepatitis virus but do not suffice to achieve sterile immunity. To determine the lag between T-cell priming and optimal activity within the CNS, the accumulation of virus-specific CD8+ T cells in the CNS relative to that in peripheral lymphoid organs was assessed by using gamma interferon-specific ELISPOT assays and class I tetramer staining. Virus-specific CD8+ T cells were first detected in the cervical lymph nodes. Expansion in the spleen was delayed and less pronounced but also preceded accumulation in the CNS. The data further suggest peripheral acquisition of cytolytic function, thus enhancing CD8+-T-cell effector function upon cognate antigen recognition in the CNS.

scholarly journals Role of CD25+ CD4+ T cells in acute and persistent coronavirus infection of the central nervous system

Virology ◽  
2013 ◽  
Vol 447 (1-2) ◽  
pp. 112-120 ◽  
Author(s):  
Maria Teresa P. de Aquino ◽  
Shweta S. Puntambekar ◽  
Carine Savarin ◽  
Cornelia C. Bergmann ◽  
Timothy W. Phares ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd4 T Cells ◽  
The Central Nervous System ◽  
Coronavirus Infection

scholarly journals Failure to Suppress the Expansion of the Activated Cd4 T Cell Population in Interferon γ–Deficient Mice Leads to Exacerbation of Experimental Autoimmune Encephalomyelitis

2000 ◽  
Vol 192 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Cong-Qiu Chu ◽  
Susan Wittmer ◽  
Dyana K. Dalton
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd4 T Cells ◽  
Wild Type ◽  
Autoimmune Encephalomyelitis ◽  
Ifn Γ ◽  
Experimental Autoimmune

Mice deficient in interferon (IFN)-γ or IFN-γ receptor develop progressive and fatal experimental autoimmune encephalomyelitis (EAE). We demonstrate that CD4 T cells lacking IFN-γ production were required to passively transfer EAE, indicating that they were disease-mediating cells in IFN-γ knockout (KO) mice. IFN-γ KO mice accumulated 10–16-fold more activated CD4 T cells (CD4+CD44hi) than wild-type mice in the central nervous system during EAE. CD4+CD44hi T cells in the spleen and central nervous system of IFN-γ KO mice during EAE showed markedly increased in vivo proliferation and significantly decreased ex vivo apoptosis compared with those of wild-type mice. IFN-γ KO CD4+CD44hi T cells proliferated extensively to antigen restimulation in vitro and accumulated larger numbers of live CD4+ CD44hi T cells. IFN-γ completely suppressed proliferation and significantly induced apoptosis of CD4+CD44hi T cells responding to antigen and hence inhibited accumulation of live, activated CD4 T cells. We thus present novel in vivo and in vitro evidence that IFN-γ may limit the extent of EAE by suppressing expansion of activated CD4 T cells.

Maintenance of CD8+T Cells during Acute Viral Infection of the Central Nervous System Requires CD4+T Cells But Not Interleukin-2

2005 ◽  
Vol 18 (1) ◽  
pp. 162-169 ◽  
Author(s):  
Jiehao Zhou ◽  
David R. Hinton ◽  
Stephen A. Stohlman ◽  
Chih-Pin Liu ◽  
Lingwen Zhong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Viral Infection ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Interleukin 2 ◽  
Acute Viral Infection ◽  
The Central Nervous System
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