ovalbumin has been researched along with Demyelinating-Diseases* in 8 studies
8 other study(ies) available for ovalbumin and Demyelinating-Diseases
Article | Year |
---|---|
Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination.
Oligodendrocyte precursor cells (OPCs) are abundant in the adult central nervous system, and have the capacity to regenerate oligodendrocytes and myelin. However, in inflammatory diseases such as multiple sclerosis (MS) remyelination is often incomplete. To investigate how neuroinflammation influences OPCs, we perform in vivo fate-tracing in an inflammatory demyelinating mouse model. Here we report that OPC differentiation is inhibited by both effector T cells and IFNγ overexpression by astrocytes. IFNγ also reduces the absolute number of OPCs and alters remaining OPCs by inducing the immunoproteasome and MHC class I. In vitro, OPCs exposed to IFNγ cross-present antigen to cytotoxic CD8 T cells, resulting in OPC death. In human demyelinated MS brain lesions, but not normal appearing white matter, oligodendroglia exhibit enhanced expression of the immunoproteasome subunit PSMB8. Therefore, OPCs may be co-opted by the immune system in MS to perpetuate the autoimmune response, suggesting that inhibiting immune activation of OPCs may facilitate remyelination. Topics: Animals; Antigen-Presenting Cells; Antigens; Astrocytes; Caspase 3; Caspase 7; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Differentiation; Central Nervous System; Cytokines; Demyelinating Diseases; Disease Models, Animal; Gene Expression; Histocompatibility Antigens Class I; Humans; Interferon-gamma; Mice; Mice, Inbred C57BL; Mice, Transgenic; Multiple Sclerosis; Myelin Sheath; Oligodendrocyte Precursor Cells; Oligodendroglia; Ovalbumin; Remyelination; T-Lymphocytes | 2019 |
TLR signals license CD8 T cells to destroy oligodendrocytes expressing an antigen shared with a Listeria pathogen.
Increasing evidence suggests a role of CD8 T cells in autoimmune demyelinating CNS disease, which, however, is still controversially discussed. Mice, which express ovalbumin (OVA) as cytosolic self-antigen in oligodendrocytes (ODC-OVA mice), respond to CNS infection induced by OVA-expressing attenuated Listeria with CD8 T cell-mediated inflammatory demyelination. This model is suitable to decipher the contribution of CD8 T cells and the pathogen in autoimmune CNS disease. Here, we show that both antigen and pathogen are required in the CNS for disease induction, though not in a physically linked fashion. Intracerebral challenge with combined toll like receptor (TLR) TLR2 and TLR9 as well as TLR7 and TLR9 agonists substituted for the bacterial stimulus, but not with individual TLR agonists (TLR2, TLR3,TLR5,TLR7, TLR9). Furthermore, MyD88 inactivation rendered ODC-OVA mice resistant to disease induction. Collectively, CD8 T cell-mediated destruction of oligodendrocytes is activated if (i) an antigen shared with an infectious agent is provided in the CNS microenvironment and (ii) innate immune signals inform the CNS microenvironment that pathogen removal warrants an immune attack by CD8 T cells, even at the expense of locally restricted demyelination. Topics: Animals; Antigens; Autoimmune Diseases; CD8-Positive T-Lymphocytes; Cells, Cultured; Central Nervous System; Demyelinating Diseases; Listeria monocytogenes; Listeriosis; Mice, Inbred C57BL; Myeloid Differentiation Factor 88; Oligodendroglia; Ovalbumin; Signal Transduction; Toll-Like Receptors | 2019 |
IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking.
IFN-gamma-inducible protein 10 (IP-10, CXCL10), a chemokine secreted from cells stimulated with type I and II IFNs and LPS, is a chemoattractant for activated T cells. Expression of IP-10 is seen in many Th1-type inflammatory diseases, where it is thought to play an important role in recruiting activated T cells into sites of tissue inflammation. To determine the in vivo function of IP-10, we constructed an IP-10-deficient mouse (IP-10(-/-)) by targeted gene disruption. Immunological analysis revealed that IP-10(-/-) mice had impaired T cell responses. T cell proliferation to allogeneic and antigenic stimulation and IFN-gamma secretion in response to antigenic challenge were impaired in IP-10(-/-) mice. In addition, IP-10(-/-) mice exhibited an impaired contact hypersensitivity response, characterized by decreased ear swelling and reduced inflammatory cell infiltrates. T cells recovered from draining lymph nodes also had a decreased proliferative response to Ag restimulation. Furthermore, IP-10(-/-) mice infected with a neurotropic mouse hepatitis virus had an impaired ability to control viral replication in the brain. This was associated with decreased recruitment of CD4(+) and CD8(+) lymphocytes into the brain, reduced levels of IFN-gamma and the IFN-gamma-induced chemokines monokine induced by IFN-gamma (Mig, CXCL9) and IFN-inducible T cell alpha chemoattractant (I-TAC, CXCL11) in the brain, decreased numbers of virus-specific IFN-gamma-secreting CD8(+) cells in the spleen, and reduced levels of demyelination in the CNS. Taken together, our data suggest a role for IP-10 in both effector T cell generation and trafficking in vivo. Topics: Animals; Antigens; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Movement; Chemokine CXCL10; Chemokines, CXC; Coronavirus Infections; Demyelinating Diseases; Dermatitis, Contact; Down-Regulation; Encephalomyelitis; Growth Inhibitors; Interferon-gamma; Isoantigens; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocyte Depletion; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Murine hepatitis virus; Mutagenesis, Site-Directed; Ovalbumin; Spleen | 2002 |
CD8-deficient SJL mice display enhanced susceptibility to Theiler's virus infection and increased demyelinating pathology.
Theiler's murine encephalomyelitis virus (TMEV) infection of the central nervous system (CNS) induces a chronic, progressive demyelinating disease in susceptible mouse strains characterized by inflammatory mononuclear infiltrates and spastic hind limb paralysis. Our lab has previously demonstrated a critical role for TMEV- and myelin-specific CD4(+) T cells in initiating and perpetuating this pathology. It has however, also been shown that the MHC class I loci are associated with susceptibility/resistance to TMEV infection and persistence. For this reason, we investigated the contribution of CD8(+) T cells to the TMEV-induced demyelinating pathology in the highly susceptible SJL/J mouse strain. Here we show that beta2M-deficient SJL mice have similar disease incidence rates to wild-type controls, however beta2M-deficient mice demonstrated earlier onset of clinical disease, elevated in vitro responses to TMEV and myelin proteolipid (PLP) epitopes, and significantly higher levels of CNS demyelination and macrophage infiltration at 50 days post-infection. beta2M-deficient mice also displayed a significant elevation in persisting viral titers, as well as an increase in macrophage-derived pro-inflammatory cytokine mRNA expression in the spinal cord at this same time point. Taken together, these results indicate that CD8(+) T cells are not required for clinical or histologic disease initiation or progression in TMEV-infected SJL mice. Rather, these data stress the critical role of CD4(+) T cells in this capacity and further emphasize the potential for CD8(+) T cells to contribute to protection from TMEV-induced demyelination. Topics: Amino Acid Sequence; Animals; Antigens, Viral; beta 2-Microglobulin; Brain; Capsid; Capsid Proteins; Cardiovirus Infections; CD4-Positive T-Lymphocytes; CD8 Antigens; CD8-Positive T-Lymphocytes; Cytokines; Demyelinating Diseases; Epitopes; Female; Genetic Predisposition to Disease; Hypersensitivity, Delayed; Inflammation Mediators; Macrophages; Mice; Mice, Inbred Strains; Mice, Knockout; Molecular Sequence Data; Myelin Proteolipid Protein; Ovalbumin; Peptide Fragments; RNA, Messenger; Spinal Cord; Theilovirus | 2001 |
Lymphocytes from mice chronically infected with Theiler's murine encephalomyelitis virus produce demyelination of organotypic cultures after stimulation with the major encephalitogenic epitope of myelin proteolipid protein. Epitope spreading in TMEV infec
Theiler's murine encephalomyelitis virus (TMEV) infection produces a chronic inflammatory disease of the spinal cord white matter, with striking similarities to both experimental allergic encephalomyelitis (EAE) and human multiple sclerosis (MS). The first phase of demyelination in this model appears to be dependent on a delayed-type hypersensitivity (DTH) response to viral antigens, driven by CD4+, Th1 lymphocytes. Macrophages, recruited in the infected CNS, would be responsible for most of the myelin damage. Recently, new populations of CD4+ lymphocytes were demonstrated in infected mice, this time with specificity for myelin antigens, particularly PLP. This suggests that, in the chronic phase of the disease, an autoimmune mechanism of demyelination, similar to EAE, may participate in the process of myelin destruction. The present study represents a first step in exploring the functional activity of these anti-myelin lymphocytes that emerge during the chronic phase of the disease. Lymphocytes were removed from chronically infected animals, they were stimulated with the major PLP encephalitogenic epitope for SJL/J mice, and they were added to organotypic myelinated spinal cord cultures for different lengths of time. Results show that lymphocytes stimulated with the major PLP epitope have a powerful capacity for demyelinating these cultures, while MBP stimulated lymphocytes and lymphocytes from control animals do not. This study, suggests that the anti-myelin response that emerges during the chronic phase of the infection is functionally active. A similar phenomenon of epitope spreading from virus to organ specific antigens may take place in humans and be involved in a number of immune-mediated diseases, including MS. Topics: Animals; Cardiovirus Infections; Cells, Cultured; Chronic Disease; Demyelinating Diseases; Encephalitis; Epitopes; Immunization; Lymphocytes; Mice; Mice, Inbred Strains; Myelin Basic Protein; Myelin Proteolipid Protein; Myelin Sheath; Organ Culture Techniques; Ovalbumin; Theilovirus | 2000 |
Passive transfer of demyelination by serum or IgG from chronic inflammatory demyelinating polyneuropathy patients.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is regarded as an autoimmune disorder, but no clearly defined autoimmune mechanism has been described. Although most patients respond to plasma exchange, no convincing role for autoantibodies has yet been demonstrated. In this study, we have successfully passively transferred disease using sera and purified IgG from 4 of 12 patients responsive to plasma exchange by bypassing the blood-nerve barrier by intraneural injection or opening it by activated T cells. The sera from CIDP patients or purified IgG produced marked conduction block and demyelination, but normal sera or IgG or that from patients with multiple sclerosis or other neuropathies did not. These observations strongly support an important role for anti-myelin/Schwann cell autoantibodies in the pathogenesis of CIDP at least in some patients. Topics: Action Potentials; Adolescent; Adoptive Transfer; Adult; Aged; Animals; Blood Transfusion; Complement C3d; Demyelinating Diseases; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Male; Middle Aged; Muscle, Skeletal; Neural Conduction; Ovalbumin; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Rats; Rats, Inbred Lew; Sciatic Nerve; Transplantation, Heterologous | 2000 |
Effect of immunization with Theiler's virus on the course of demyelinating disease.
Intracerebral (i.c.) inoculation of susceptible mice with Theiler's murine encephalomyelitis virus (TMEV) results in a demyelinating disease similar to human multiple sclerosis (MS). Mice develop a strong immune response to TMEV and the disease is believed to be immune-mediated. In order to investigate the effects of the immune response to TMEV on the course of demyelination, we immunized host mice with UV-inactivated TMEV at various time periods in relation to intracerebral inoculation with live TMEV. Here, we show that subcutaneous immunization of mice with TMEV prior to infection with virus is able to protect susceptible, SJL/J mice from demyelinating disease. This protective effect appears to be long-lasting; immunization greater than 90 days prior to i.c. inoculation of the virus protects mice from subsequent infection. However, immunization of mice after i.c. infection with TMEV does not confer protection, but rather exacerbates the disease symptoms. Thus, this system offers a model for studying viral capsid proteins and/or epitopes which are involved in either protection from disease or immune-mediated pathogenesis leading to myelin destruction in susceptible mice. Topics: Animals; Demyelinating Diseases; Disease Susceptibility; Immunization; Maus Elberfeld virus; Mice; Mice, Inbred Strains; Myelin Sheath; Ovalbumin; Time Factors; Ultraviolet Rays; Vaccines, Inactivated | 1993 |
Acute demyelination in EAE after pretreatment with foreign protein and muramyl dipeptide (MDP).
Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Brain; Demyelinating Diseases; Encephalomyelitis, Autoimmune, Experimental; Freund's Adjuvant; Guinea Pigs; Myelin Sheath; Nerve Degeneration; Ovalbumin; Spinal Cord | 1984 |