myelin-basic-protein and Vaccinia

Its proof, significance, and the cellular cross reactivity to basic encephalitogenic protein of vaccinia-stimulated T-cells. Vaccination against smallpox induces both, a cellular allergy and immunity, and the production of humoral antibodies. Of greater importance for the defense of the organism against infections by orthopox viruses is the cellular immunity. New methods for the proof of cellular immunity and an in vitro-technique for its examination by challange with variola vera virus are described. In close connection with induction of cellular allergy by vaccination an immunological cell-bound reactivity of isolated lymphocytes develops against the basic encephalitogenic protein. In this antigen-stimulated resp.-irritated stage isolated lymphocytes show an enhanced rate of chromosomal aberrations and a high rate of spontaneous transformations. Lymphocytes of patients with Multiple Sclerosis demonstrate a high stimulation rate (3H- resp. 14C-Thymidine-inlay) after challenge with antigen of vaccinia virus. The T cell-mediated cross reactivity between vaccinia and myelin extracts is discussed as an hypothetic pathogenic factor of CNS complications after primary smallpox vaccination.

Topics: Antigen-Antibody Reactions; Cell Migration Inhibition; Child; Cross Reactions; Encephalomyelitis, Acute Disseminated; Epitopes; Humans; Immunity, Cellular; Immunization, Passive; Lymphocyte Activation; Myelin Basic Protein; Poxviridae Infections; Skin Tests; Smallpox; T-Lymphocytes; Vaccination; Vaccinia

Multiple sclerosis is an inflammatory, demyelinating, central nervous system disease mediated by myelin-specific T cells. Environmental triggers that cause the breakdown of myelin-specific T cell tolerance are unknown. Here we found that CD8(+) myelin basic protein (MBP)-specific T cell tolerance was broken and autoimmunity was induced by infection with a virus that did not express MBP cross-reactive epitopes and did not depend on bystander activation. Instead, the virus activated T cells expressing dual T cell antigen receptors (TCRs) that were able to recognize both MBP and viral antigens. Our results demonstrate the importance of dual TCR-expressing T cells in autoimmunity and suggest a mechanism by which a ubiquitous viral infection could trigger autoimmunity in a subset of infected people, as suggested by the etiology of multiple sclerosis.

Topics: Animals; Antigen Presentation; Autoimmunity; CD8-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Central Nervous System; Disease Models, Animal; Epitopes, T-Lymphocyte; Histocompatibility Antigens; Humans; Lymphocyte Activation; Mice; Mice, Transgenic; Multiple Sclerosis; Myelin Basic Protein; Peptide Fragments; Receptors, Antigen, T-Cell; Self Tolerance; Transgenes; Vaccinia; Vaccinia virus

Topics: Animals; CD8-Positive T-Lymphocytes; Disease Susceptibility; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Mice, Transgenic; Molecular Mimicry; Multiple Sclerosis; Myelin Basic Protein; Receptors, Antigen, T-Cell; Self Tolerance; Vaccinia; Vaccinia virus

A primary demyelinating form of experimental allergic encephalomyelitis (EAE) resembling human multiple sclerosis (MS) occurs in Callithrix jacchus marmosets following immunization with human white matter. Participation of a T-cell immune response against myelin basic protein (MBP) in this disease model is supported by observations of increased reactivity against MBP in PBMC and of adoptive transfer of an inflammatory form of EAE by MBP-reactive T-cells. To evaluate the effects of ectopic presentation of MBP on marmoset EAE, animals were vaccinated prior to induction of EAE by subcutaneous injection of attenuated strains of vaccinia virus genetically engineered to contain either the entire coding sequence for human MBP (vT15) or the equine herpes virus glycoprotein gH gene (vAbT249). Vaccination with vT15 was followed by transient cytoplasmic and surface membrane expression of MBP in circulating PBMC (15-45 days). The onset of clinical EAE after immunization (pi) was markedly delayed in vT15-vaccinated animals (37-97 days pi, n = 4) compared to vAbT249-vaccinated controls (14-18 days pi, n = 3). Proliferative responses against MBP but not against vaccinia antigens or phytohemagglutinin were suppressed in protected animals. Thus, development of attenuated live viruses carrying genes for myelin antigens could be useful for induction of immunologic tolerance and for modulation of autoimmune demyelination.

Topics: Animals; Antibodies; Antibodies, Viral; Antibody Formation; Antigens, Viral; Callithrix; Encephalomyelitis, Autoimmune, Experimental; Myelin Basic Protein; Vaccination; Vaccines, Synthetic; Vaccinia; Vaccinia virus; Viral Vaccines

Twelve-day-old cultures of dissociated newborn mouse brain were infected with neurotropic vaccinia virus strain WR. Using the indirect immuno-fluorescence staining technique the total destruction of galactocerebroside (GL) or myelin basic protein (MBP)-positive oligodendrocytes could be detected after 72 h of infection. The activity of the oligodendrocyte-specific enzymes, cerebroside sulfotransferase (CST) and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNP), was 27% and 17% respectively of the activity in noninfected controls. This reduction was not a result of viral-induced inhibition of host protein synthesis. In cultures treated with puromycin GC- and MBP- positive oligodendrocytes were detectable at a time at which no CST or CNP activity could detected.

Topics: 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Animals, Newborn; Brain; Cells, Cultured; Encephalitis; Galactosylceramides; Mice; Myelin Basic Protein; Neuroglia; Oligodendroglia; Phosphoric Diester Hydrolases; Puromycin; Sulfotransferases; Sulfurtransferases; Vaccinia; Vaccinia virus

Topics: Animals; Autoantibodies; Distemper; Distemper Virus, Canine; Dogs; Encephalitis; Mice; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Vaccinia; Vaccinia virus

After intracranial replication of a neurotropic strain of vaccinia in mouse brain, analysis of the purified virus preparation reveals the presence of at least one host protein on the virus which was identified as the myelin basic protein. Vaccinia virus Elstree, a dermotropic virus may substitute for complete Freund's adjuvant (CFA) in inducing experimental allergic encephalomyelitis (EAE). Guinea pigs challenged with virus-myelin emulsions without CFA developed clinical and histological signs of EAE.

Topics: Adjuvants, Immunologic; Animals; Brain; Disease Models, Animal; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental; Guinea Pigs; Mice; Myelin Basic Protein; Vaccinia; Vaccinia virus

Topics: Animals; Antibodies, Viral; Autoantibodies; Brain; Encephalomyelitis, Autoimmune, Experimental; Guinea Pigs; Immunity, Cellular; Myelin Basic Protein; Vaccinia

Vaccinia virus infection was performed by scarification of the shaved skin (5 times 5 cm2) on the back of Pirbright guinea pigs. The macrophage migration inhibition test was performed with peritonealexudate cells 7, 11, 14 and 21 days after infection. Macrophage migration inhibition occurred after exposure of the cells to whole brain tissue antigen on the 7th, 11th, 14th day after infection (s. table 1). Lymphocyte transformation responses were examined by 14C-2-Thymidin uptake using blood cultures and basic encephalitogenic protein and whole brain tissue extract as antigens. A positive transformation response could be demonstrated from one to 8 weeks after infection (s. table 2). The specificity of the transformation response to brain antigen was established using control cultures stimulated with PHA or PPD. In no case stimulation occured with PPD. Stimulation with PHA was not altered. On the other hand the spontaneous lymphocyte transformation was enhanced at one week after infection and lymphocyte cultures exposed to heat inactivated vaccinia virus showed transformation from the 3th week after infection until the end of the observation period (i.e. 8 weeks) (s. table 2). The reason why cell mediated hypersensitivity to brain antigen is induced following vaccinia infection remains unknown. The most probable among several possible mechanisms seem a) the induction of virus-specific antigens on the surface of infected cells or b) the release of brain specific antigen through virus infection.

Topics: Administration, Topical; Animals; Antigens; Brain; Brain Diseases; Cell Migration Inhibition; Central Nervous System Diseases; Guinea Pigs; Immunity, Cellular; Immunization; Lectins; Lymphocyte Activation; Macrophage Migration-Inhibitory Factors; Macrophages; Myelin Basic Protein; Skin; Tuberculin; Vaccinia

29 guinea pigs, strain Pirbright, were infected with vaccinia virus, strain Elstree, by the dermal route. The observation period was 14 days. Thereafter, the animals were killed and their central nervous systems (CNS) histologically and immunohistologically, the blood fluorescence-serologically examined. Histological examination revealed meningitis, ependymitis or disseminated meningoencephalitis with slight perivascular cuffing in 72% of the animals. The viral antigen was found in 3 animals (10%). It was present most often in the cytoplasma of the arachnoidal and/or ependymal cells, as well as in the cells of the vessel walls and less often in the glial and/or nerve cells. The infected cells showed no severe degenerative changes. The blood-brain-barrier displayed localized disturbances. The examination of the myelin sheaths revealed disseminated foci of disappearance of myelin fluorescence in the perivascular, paraventricular and subcortical regions. Antibodies directed against myelin sheaths, or nerve cells could be detected in the sera of 48% of the animals. The results give evidence that the vaccinia infection is capable to induce a potentially pathogenic autoimmune reaction directed against brain. Such an immunomechanism can be triggered without any signs of acute lytic infection of the CNS. The mechanism and significance of this reaction are discussed.

Topics: Animals; Antibodies; Antibody Formation; Antigens; Autoimmune Diseases; Blood-Brain Barrier; Brain; Central Nervous System Diseases; Cerebrovascular Disorders; Ependyma; Guinea Pigs; Immune Sera; Immunity; Immunoglobulin G; Meningitis; Myelin Basic Protein; Vaccinia