Biomaterial Database

Inhibition of Theiler's virus-mediated demyelination by peripheral immune tolerance induction. 1995

W J Karpus, and J G Pope, and J D Peterson, and M C Dal Canto, and S D Miller

Department of Microbiology, Northwestern University Medical School, Chicago, IL 60611, USA.

Theiler's murine encephalomyelitis virus (TMEV), a member of the cardiovirus subfamily of the Picornaviridae, is a natural pathogen of mice. Thirty to 60 days following intracerebral infection with TMEV, susceptible inbred mouse strains develop a chronic, progressive, T cell-mediated inflammatory demyelinating disease of the central nervous system (CNS) characterized by spastic hind limb paralysis and a lifelong persistent CNS virus infection. We have examined the effect of peripheral virus-specific tolerance on the development of demyelinating disease. Treatment of SJL/J mice with TMEV-coupled, ethyl carbodiimide-treated splenocytes either before or after infection with live TMEV prevented the development of clinical disease, including inflammation and demyelination in the CNS. Prevention of clinical disease was paralleled by significant reductions in virus-specific immune responses, including delayed type hypersensitivity and T cell proliferative responses. Tolerance induction resulted in a significant reduction in the absolute numbers of mononuclear cells infiltrating the CNS, particularly the CD4+IL-2R+ T cell subset, 3, 5, and 8 wk postinfection. In contrast, tolerance induction had no effect on the numbers of CD8+IL-2R+ T cells infiltrating the CNS. Treatment with TMEV-coupled splenocytes failed to prevent the development of relapsing experimental autoimmune encephalomyelitis, demonstrating the specificity of in vivo tolerance induction. Prevention of demyelinating disease did not correlate with the increased TMEV-specific Ab responses observed in tolerized mice. These results indicate that induction of immune tolerance to TMEV can down-regulate a chronic immunopathogenic disease directed against virus Ag persisting in the CNS that normally results in a progressive demyelinating disease similar to multiple sclerosis.

UI	MeSH Term	Description	Entries
D007108	Immune Tolerance	The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.	Immunosuppression (Physiology),Immunosuppressions (Physiology),Tolerance, Immune
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D002490	Central Nervous System	The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.	Cerebrospinal Axis,Axi, Cerebrospinal,Axis, Cerebrospinal,Central Nervous Systems,Cerebrospinal Axi,Nervous System, Central,Nervous Systems, Central,Systems, Central Nervous
D003711	Demyelinating Diseases	Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system.	Clinically Isolated CNS Demyelinating Syndrome,Clinically Isolated Syndrome, CNS Demyelinating,Demyelinating Disorders,Demyelination,Demyelinating Disease,Demyelinating Disorder,Demyelinations
D005260	Female		Females
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013154	Spleen	An encapsulated lymphatic organ through which venous blood filters.
D014765	Viral Vaccines	Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.	Viral Vaccine,Vaccine, Viral,Vaccines, Viral
D016176	T-Lymphocyte Subsets	A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.	T-Cell Subset,T-Cell Subsets,T-Lymphocyte Subset,Subset, T-Cell,Subset, T-Lymphocyte,Subsets, T-Cell,Subsets, T-Lymphocyte,T Cell Subset,T Cell Subsets,T Lymphocyte Subset,T Lymphocyte Subsets
D016219	Immunotherapy, Adoptive	Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)	Adoptive Cellular Immunotherapy,Adoptive Immunotherapy,CAR T-Cell Therapy,Cellular Immunotherapy, Adoptive,Chimeric Antigen Receptor Therapy,Immunotherapy, Adoptive Cellular,Adoptive Cellular Immunotherapies,Adoptive Immunotherapies,CAR T Cell Therapy,CAR T-Cell Therapies,Cellular Immunotherapies, Adoptive,Immunotherapies, Adoptive,Immunotherapies, Adoptive Cellular,T-Cell Therapies, CAR,T-Cell Therapy, CAR,Therapies, CAR T-Cell,Therapy, CAR T-Cell