Myelin encephalomyelitis

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

Some aspects of multiple sclerosis are reflected in the animal model experimental autoimmune encephalomyelitis, which is induced by immunization of susceptible animals with appropriate encephalogenic proteins or peptides. In these animals, if cultured adult stem cell neurospheres are injected into the bloodstream, injected cells can find their way to damaged portions of the nervous system and improve function in mice. How the injected cells augmented the recovery process is unclear. One possibility is that cells recruited to the lesions differentiated into oligodendrocytes and generated new myelin sheaths, but this seems unlikely in the face of ongoing cellular destruction. 

Other acquired disorders affecting myelin in humans may be secondary to viral infections, neoplasias or immunosuppressive therapy. Acute disseminated encephalomyelitis, also called postinfectious or postimmunization encephalitis, represents a group of disorders usually of mixed viral-immunological etiology. The condition is most commonly related to a spontaneous viral infection, of which major examples are measles, smallpox or chickenpox [1,2]. 

Iglesias, A., Bauer, J., Litzenburger, T. etal. T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 36 220-234,2001. 

Lassmann, H. Experimental autoimmune encephalomyelitis. In R. A. Lazzarini (ed.), Myelin Biology and Disorders. San Diego, CA Elsevier Academic Press, 2004, pp. 1039-1071. 

Jiang H, Curran S, Ruiz-Vazquez E, Liang B, Winchester R, Chess L Regulatory CDS + T cells fine-tune the myelin basic protein-reactive T cell receptor V(5 repertoire during experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 2003 100 8378-8383. 

Chen Y, Inobe J, Kuchroo VK, Baron JL, Janeway CA Jr, Weiner HL Oral tolerance in myelin basic protein T-cell receptor transgenic mice suppression of autoimmune encephalomyelitis and dose-dependent induction of regulatory cells. Proc Natl Acad Sci USA 1996 93 388-391. 

Multiple sclerosis (MS) is the most frequent inflammatory demyeli-nating disease of the central nervous system that affects worldwide about 2.5 million people with no cure. Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-induced EAE) in DA rats is an appropriate model for therapeutic testing, sharing many features with human multiple sclerosis. 

Most cells of the immune system are ordinarily kept apart from those of the nervous system by means of the blood-brain barrier. However, allergic encephalomyelitis, in which T cells attack the myelin sheath of brain neurons, can easily be induced in mice.506 A similar autoimmune process is thought to be involved in human multiple sclerosis (see Chapter 30, pp. 1769, 1808, and Fig. 30-9).507,508 High levels of circulating IgM are found in some demyelinating diseases of peripheral neurons.508 In Rasmussen s encephalitis, which causes brain inflammation and epilepsy, serum antibodies attack a glutamate receptor subunit GluR3.509... 

Grogan, J.L., Kramer, A., Nogai, A., et al. (1999) Cross-reactivity of myelin basic protein-specific T cells with multiple microbial peptides Experimental autoimmune encephalomyelitis induction in TCR transgenic mice. J. Immunol. 163, 3764-3770. 

Lider, O., Santos., L. M., Lee, C. S., Higgins, P. J., and Weiner, H. L. 1989. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein, II. Suppression of disease and in vitro immune responses is mediated by antigen-specific CD8+ T lymphocytes. J. Immunol 142 748-752. 

Stefferl, A., Schubart, A., Storch, M., Amini, A., Mather, I., Lassmann, H., Linington, C. 2000. Butyrophilin, a milk protein, modulates the encephalitogenic T cell response to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis. J Immunol. 165, 2859-2865. 

ADEM acute disseminated encephalomyelitis is an immune mediated disease of brain. It is brief but significant and results in direct myelin damage. It usually occurs following a viral infection or vaccination (commonly for measles, mumps or rubella), but it may also appear spontaneously. 

Linington C, Bradl M, Lassmann H, Brunner C, Vass K (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 130 443 54. 

Dal Canto MC, Calenoff M A, Miller SD, Vanderlugt CL (2000) 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 infection has functional activity. J Neuroimmunol 104 79-84. 

Harling-Berg, C. J., Knopf, P. M., and Cserr, H.F., Myelin basic protein infused into cerebrospinal fluid suppresses experimental autoimmune encephalomyelitis,... 

Perry, L. L., Barzaga-Gilbert, E., and Trotter, J. L., T cell sensitization to proteolipid protein in myelin basic protein inducing relapsing experimental allergic encephalomyelitis. J. Neuroimmunol., 33, 7, 1991. 

---