Abstract
(SJL/J × PL/J)F1 mice immunized with myelin basic protein (MBP) develop an autoimmune demyelinating disease termed relapsing experimental allergic encephalomyelitis (rEAE). The acute stage of disease is mediated by CD4+ T cells specific for MBP amino acids 1–9. To determine the immunologic bases for disease relapse, host sensitization to additional autoantigens of the central nervous system was measured. Results indicate that most animals develop T cell reactivity to endogenous myelin proteolipid protein (PLP) during rEAE. However, PLP-specific immunity does not appear to accound for expression of relapse episodes of demyelination. relapse episodes of demyelination.
Keywords: Encephalomyelitis, Myelin basic protein, Proteolipid protein, Multiple sclerosis, (Mouse)
References
- Acha-Orbea H., Mitchell D.J., Timmermann L., Wraith D.C., Tausch G.S., Waldor M.K., Zamvil S.S., McDevitt H.O., Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allos specific immune intervention. Cell. 1988;54:263–273. doi: 10.1016/0092-8674(88)90558-2. [DOI] [PubMed] [Google Scholar]
- Albrecht P., Tourtellotte W.W., Hicks J.T., Sato H., Boone E.J., Potvin A.R. Intra-blood-brain barrier measles virus antibody synthesis in multiple sclerosis patients. Neurology. 1983;33:45–50. doi: 10.1212/wnl.33.1.45. [DOI] [PubMed] [Google Scholar]
- Allegretta M., Nicklas J.A., Sriram S., Albertini R.J. T cells responsive to myelin basic protein in patients with multiple sclerosis. Science. 1990;247:718–721. doi: 10.1126/science.1689076. [DOI] [PubMed] [Google Scholar]
- Alvord E.C., Kies M.W., Suckling A.J. Alan R. Liss; New York: 1984. Experimental Allergic Encephalomyelitis: A Useful Model for Multiple Sclerosis. [Google Scholar]
- Baxevanis C.N., Reclos G.J., Servis C., Anastasopoulos E., Arsenis P., Katsiyiannis A., Matikas N., Lambris J.D., Papamichail M. Peptides of myelin basic protein stimulate T lymphocytes from patients with multiple sclerosis. J. Neuroimmunol. 1989;22:23–30. doi: 10.1016/0165-5728(89)90005-2. [DOI] [PubMed] [Google Scholar]
- Burks J.S., DeVald B.L., Jankovsky L.D., Gerdes J.C. Two coronaviruses isolated from central nervous system tissue of two multiple sclerosis patients. Science. 1980;209:933–934. doi: 10.1126/science.7403860. [DOI] [PubMed] [Google Scholar]
- Butter C., Healry D.G., Agha N., Turk J.L. An immunoelectron microscopical study of the expression of class II MHC and a T lymphocyte surfac marker during chronic relapsing experimental allergic encephalomyelitis. J. Neuroimmunol. 1988;20:45–51. doi: 10.1016/0165-5728(88)90113-0. [DOI] [PubMed] [Google Scholar]
- Cambi F., Lees M.B., Williams R.M., Macklin W.B. Chronic experimental allergic encephalomyelitis produced by bovine proteolipid apoprotein: immunological studies in rabbits. Ann. Neurol. 1983;13:303. doi: 10.1002/ana.410130313. [DOI] [PubMed] [Google Scholar]
- Catz I., Warren K.G. Intrathecal synthesis of autoantibodies to myelin basoc protein in multiple sclerosis. Can. J. Neurol. Sci. 1986;13:21–24. doi: 10.1017/s0317167100035745. [DOI] [PubMed] [Google Scholar]
- Chou F.C.-H., Chou C.-H.J., Shapira R., Kibler R.F. Basis of microheterogeneity of myelin basic protein. J. Biol. Chem. 1976;251:2671–2679. [PubMed] [Google Scholar]
- Cohen S.R., McKhann G.M., Guarnieri M. A radioimmunoassay for myelin basic protein and its use for quantitative measurements. J. Neurochem. 1975;25:371. doi: 10.1111/j.1471-4159.1975.tb04329.x. [DOI] [PubMed] [Google Scholar]
- Cook S., Blumberg B., Dowling P.C. Potential role of paramyxoviruses in multiple sclerosis. Neurol. Clin. 1986;4:303–319. doi: 10.1016/S0733-8619(18)31000-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coyle P.K., Sibony P.A. Viral specificity of multiple sclerosis tear immunoglobulins. J. Neuroimmunol. 1987;14:197–203. doi: 10.1016/0165-5728(87)90054-3. [DOI] [PubMed] [Google Scholar]
- Endoh M., Tabira T., Kunishita T., Sakai K., Yamamura T., Taketomi T. DM-20, a proteolipid apoprotein, is an encephalitogen of acute and relapsing autoimmune encephalitis in mice. J. Immunol. 1986;137:3832. [PubMed] [Google Scholar]
- Fritz R.B., McFarlin D.E. Encephalitogenic epitopes of myelin basic protein. Chem. Immunol. 1989;46:101–125. [PubMed] [Google Scholar]
- Fritz R.B., Chou C.H., McFarlin D.E. Relapsing murine experimental allergic encephalomyelitis induced by myelin basic protein. J. Immunol. 1983;130:1024–1026. [PubMed] [Google Scholar]
- Fritz R.B., Chou C.H., McFarlin D.E. Induction of experimental allergic encephalomyelitis in PL/J and (SJL/J × PL/J)F1 mice by myelin basic protein and its peptides: localization of a second encephalitogenic determinant. J. Immunol. 1983;130:191–194. [PubMed] [Google Scholar]
- Fritz R.B., Perry L.L., Chou C.-H.J. Genetic control of myelin basic protein-induced experimental allergic encephalomyelitis in mice. Prog. Clin. Biol. Res. 1984;146:235–242. [PubMed] [Google Scholar]
- Fritz R.B., Skeen M.J., Chou C.H., Garcia M., Egorov I.K. Major histocompatibility complex-linked control of the murine immune response to myelin basic protein. J. Immunol. 1985;134:2328–2332. [PubMed] [Google Scholar]
- Fritz R.B., Skeen M.J., Chou C.-H.J., Zamvil S.S. Localization of an encephalitogenic epitope for the SJL mouse in the N-terminal region of myelin basic protein. J. Neuroimmunol. 1990;26:239–243. doi: 10.1016/0165-5728(90)90006-9. [DOI] [PubMed] [Google Scholar]
- Garcia-Merino A., Persson M.A., Ernerudh J., Diaz-Gil J.J., Olsson T. Serum and cerebrospinal fluid antibodies against myelin basic protein and their IgG subclass distribution in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 1986;49:1066–1070. doi: 10.1136/jnnp.49.9.1066. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goswami K.K., Randall R.E., Lange L.S., Russell W.C. Antibodies against the paramyxovirus SV5 in the cerebrospinal fluids of some multiple sclerosis patients. Nature. 1987;327:244–247. doi: 10.1038/327244a0. [DOI] [PubMed] [Google Scholar]
- Haegert D.G., Michaud M., Schwab C., Francis G.S. Multiple sclerosis and HLA class II susceptibility and resistance genes. J. Neurol. Sci. 1990;26:66–73. doi: 10.1002/jnr.490260108. [DOI] [PubMed] [Google Scholar]
- Hampson D.R., Poduslo S.E. Purification of proteolipid protein and production of specific antiserum. J. Neuroimmunol. 1986;11:117–129. doi: 10.1016/0165-5728(86)90113-x. [DOI] [PubMed] [Google Scholar]
- Hinrichs D.J., Roberts C.M., Waxman F.J. Regulation of paralytic experimental allergic encephalomyelitis in rats: susceptibility to active and passive disease reinduction. J. Immunol. 1981;126:1857. [PubMed] [Google Scholar]
- Johnson D., Hafler D.A., Fallis R.J., Lees M.B., Brady R.O., Quarles R.H., Weiner H.L. Cell-mediated immunity to myelin-associated glycoprotein, proteolipid protein, and myelin basic protein in multiple sclerosis. J. Neuroimmunol. 1986;13:99–108. doi: 10.1016/0165-5728(86)90053-6. [DOI] [PubMed] [Google Scholar]
- Julius M.H., Simpson E., Herzenberg L.A. A rapid method for the isolation of functional thymus derived murine lymphocytes. Eur. J. Immunol. 1973;3:645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
- Kennedy M.K., Tan L.-J., Dal Canto M.C., Tuohy V.K., Lu Z., Trotter J.L., Miller S.D. Inhibition of murine relapsing experimental autoimmune encephalomyelitis by immune tolerance to proteolipid protein and its encephalitogenic peptides. J. Immunol. 1990;144:909–915. [PubMed] [Google Scholar]
- Kitze B., Pette M., Rohrbach E., Stadt D., Kappos L., Wekerle H. Myelin-specific T lymphocytes in multiple sclerosis patients and healthy individuals. J. Neuroimmunol. 1988;20:237. doi: 10.1016/0165-5728(88)90166-x. [DOI] [PubMed] [Google Scholar]
- Kono D.H., Urban J.L., Horvath S.J., Ando D.G., Saavedra R.A., Hood L. Two minor determinants of myelin basic protein induce experimental allergic encephalomyelitis in SJL/J mice. J. Exp. Med. 1988;168:213–227. doi: 10.1084/jem.168.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Link H., Baig S., Jiang Y.P., Olsson O., Hojeberg B., Kostulas V., Olsson T. B cells and antibodies in MS. Res. Immunol. 1989;140:219–226. doi: 10.1016/0923-2494(89)90091-6. [DOI] [PubMed] [Google Scholar]
- Lublin F.D. Relapsing experimental allergic encephalomyelitis. An autoimmune model for multiple sclerosis. Springer Semin. Immunopathol. 1985;8:197. doi: 10.1007/BF00197296. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Macklin W.B., Oberfield E., Lees M.B. Electroblot analysis of rat myelin proteolipid protein and basic protein during development. Dev. Neurosci. 1984;6:161. doi: 10.1159/000112343. [DOI] [PubMed] [Google Scholar]
- Martin R., Jaraquemada D., Flerlage M., Richert J., Whitaker J., Long E.O., McFarlin D.E., McFarland H.F. Fine specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals. J. Immunol. 1990;145:540–548. [PubMed] [Google Scholar]
- McDevitt H.O., Wraith D.C., Smilek D.E., Lundberg A.S., Steinman L. Cold Spring Harbor Symposia on Quantitative Biology. Cold Spring Harbor Laboratories; Cold Spring Harbor, NY: 1989. Evolution, function, and utilization of major histocompatibility complex polymorphism in autoimmune disease; pp. 853–857. [DOI] [PubMed] [Google Scholar]
- Oksenberg J.R., Steinman L. The role of the MHC and T-cell receptor in susceptibility to multiple sclerosis. Curr. Opin. Immunol. 1989;2:619–621. doi: 10.1016/0952-7915(90)90021-8. [DOI] [PubMed] [Google Scholar]
- Olsson T., Baig S., Hojeberg B., Link H. Antimyelin basic protein and antimyelin antibody-producing cells in multiple sclerosis. Ann. Neurol. 1990;27:132–136. doi: 10.1002/ana.410270207. [DOI] [PubMed] [Google Scholar]
- Ota K., Matsui M., Milford E.L., Mackin G.A., Weiner H.L., Hafler D.A. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature. 1990;346:183–187. doi: 10.1038/346183a0. [DOI] [PubMed] [Google Scholar]
- Panitch H., Ciccone C. Induction of recurrent experimental allergic encephalomyelitis with myelin basic protein. Ann. Neurol. 1981;9:433. doi: 10.1002/ana.410090504. [DOI] [PubMed] [Google Scholar]
- Perry L.L., Barzaga E. Kinetics and specificity of T and B cell responses in relapsing experimental allergic encephalomyelitis. J. Immunol. 1987;138:1434–1441. [PubMed] [Google Scholar]
- Perry L.L., Williams I.R. Regulation of transplantation immunity in vivo by monoclonal antibodies recognizing host class II restriction elements. I. Genetics and specificity of anti-Ia immunotherapy in murine skin allograft recipients. J. Immunol. 1985;134:2935–2941. [PubMed] [Google Scholar]
- Perry L.L., Barzaga M.E., Ferguson T.A. Modulation of experimental allergic encephalomyelitis with anti-T suppressor factor antibodies. J. Immunol. 1988;141:3016–3021. [PubMed] [Google Scholar]
- Pettinelli C.B., Fritz R.B., Chou C.-H.J., McFarlin D.E. Encephalitogenic activity of guinea pig myelin basic protein in the SJL/J mouse. J. Immunol. 1982;129:1209. [PubMed] [Google Scholar]
- Richert J.R., Reuben-Burnside C.A., Deibler G.E., Kies M.W. Fine specificities of myelin basic protein-specific human T-cell clones. Ann. N.Y. Acad. Sci. 1988;540:345–348. doi: 10.1111/j.1749-6632.1988.tb27094.x. [DOI] [PubMed] [Google Scholar]
- Sakai K., Sinha A.A., Mitchell D.J., Zamvil S.S., Rothbard J.B., McDevitt H.O., Steinman L. Vol. 85. 1988. Involvement of distinct murine T-cell receptors in the autoimmune encephalitogenic response to nested epitopes of myelin basic protein; pp. 8608–8612. (Proc. Natl. Acad. Sci. U.S.A.). [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakai K., Zamvil S.S., Mitchell D.J., Lim M., Rothbard J.B., Steinman L. Characterization of a major encephalitogenic T cell epitope in SJL/J mice with synthetic oligopeptides of myelin basic protein. J. Neuroimmunol. 1988;19:21–32. doi: 10.1016/0165-5728(88)90032-x. [DOI] [PubMed] [Google Scholar]
- Salmi A., Reunanen M., Ilonen J., Panelius M. Intrathecal antibody synthesis to virus antigens in multiple sclerosis. Clin. Exp. Immunol. 1983;52:241–249. [PMC free article] [PubMed] [Google Scholar]
- Sobel R.A., Blanchette B.W., Bhan A.K., Colvin R.B. The immunopathology of experimental allergic encephlomyelitis. I. Quantitative analysis of inflammatory cells in situ. J. Immunol. 1984;132:2393. [PubMed] [Google Scholar]
- Sobel R.A., Blanchette B.W., Bhan A.K., Colvin R.B. The immunopathology of experimental allergic encephalomyelitis. II. Endothelial cell Ia increases prior to inflammatory cell infiltration. J. Immunol. 1984;132:2402. [PubMed] [Google Scholar]
- Trotter J.L., Lieberman L., Margolis F.L., Agrawal H.C. Radioimmunoassay for central nervous system myelin specific proteolipid protein. J. Neurochem. 1981;36:1256–1262. doi: 10.1111/j.1471-4159.1981.tb01725.x. [DOI] [PubMed] [Google Scholar]
- Trotter J.L., Clark H.B., Collins K.G., Wegeschiede C.L., Scarpellani J.D. Myelin proteolipid protein induced demyelinating disease in mice. J. Neurol. Sci. 1987;79:173–188. doi: 10.1016/0022-510x(87)90271-1. [DOI] [PubMed] [Google Scholar]
- Trotter J.L., Van der Veen R.C., Hickey W.F. Is myelin proteolipid protein an MS antigen? Neurology. 1990;42:366. (Suppl.) [Google Scholar]
- Urban J.L., Kumar V., Kono D.H., Gomez C., Horvath S.J., Clayton J., Ando D.G., Sercarz E.E., Hood L. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell. 1988;54:577–592. doi: 10.1016/0092-8674(88)90079-7. [DOI] [PubMed] [Google Scholar]
- Van der Veen R.C., Trotter J.L., Hickey W.F., Kapp J.A. The development and characterization of encephalitogenic cloned T cells specific for myelin proteolipid protein. J. Neuroimmunol. 1990;26:139–145. doi: 10.1016/0165-5728(90)90085-2. [DOI] [PubMed] [Google Scholar]
- Waksman B. Mechanisms in multiple sclerosis. Nature. 1985;318:104–105. doi: 10.1038/318104a0. [DOI] [PubMed] [Google Scholar]
- Warren K.G., Catz I. A myelin basic protein antibody cascade in purified IgG from cerebrospinal fluid of multiple sclerosis patients. J. Neurol. Sci. 1990;96:19–27. doi: 10.1016/0022-510x(90)90053-p. [DOI] [PubMed] [Google Scholar]
- Weber W.E.J., Buurman W.A. Myelin basic protein-specific CD4+ cytolytic T-lymphocyte clones isolated from multiple sclerosis patients. Hum. Immunol. 1988;22:97–109. doi: 10.1016/0198-8859(88)90040-7. [DOI] [PubMed] [Google Scholar]
- Welch A.M., Holda J.H., Swanborg R.H. Regulation of experimental allergic encephalomyelitis. II. Appearance of suppressor cells during the remission phase of the disease. J. Immunol. 1980;125:186. [PubMed] [Google Scholar]
- Yamamura T., Namikawa T., Endoh M., Kunishita T., Tabira T. Experimental allergic encephalomyelitis induced by proteolipid protein in Lewis rats. J. Neuroimmunol. 1986;12:143. doi: 10.1016/0165-5728(86)90027-5. [DOI] [PubMed] [Google Scholar]
- Zamvil S., Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu. Rev. Immunol. 1990;8:579–621. doi: 10.1146/annurev.iy.08.040190.003051. [DOI] [PubMed] [Google Scholar]
- Zamvil S., Nelson P., Trotter J., Mitchell D., Knobler R., Fritz R., Steinman L. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature. 1985;317:355. doi: 10.1038/317355a0. [DOI] [PubMed] [Google Scholar]
- Zamvil S.S., Mitchell D.J., Moore A.C., Kitamura K., Steinman L., Rothbard J.B. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature. 1986;324:258–260. doi: 10.1038/324258a0. [DOI] [PubMed] [Google Scholar]
- Zamvil S.S., Mitchell D.J., Powell M.B., Sakai K., Rothbard J.B., Steinman L. Multiple discrete encephalitogenic epitopes of the autoantigen myelin basic protein include a determinant for I-E class II-restricted T cells. J. Exp. Med. 1988;168:1181–1186. doi: 10.1084/jem.168.3.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhang J.W., Chou C.H., Hashim G., Medaer R., Raus J.C. Preferential peptide specificity and HLA restriction of myelin basic protein. Cell. Immunol. 1990;129:189–198. doi: 10.1016/0008-8749(90)90197-y. [DOI] [PubMed] [Google Scholar]