title: Encephalitogenic potential of myelin basic protein-specific T cells isolated from normal rhesus macaques.
abstract: Myelin basic protein (MBP)-specific T cells are implicated in the pathogenesis of multiple sclerosis and are targets of selective immunotherapies. However, autoantigen-specific T cells can also be isolated from healthy individuals. Their functional potential is unknown and obviously cannot be tested in humans. We approached this question in a closely related primate species, the rhesus monkey. CD4+ T cell lines specific for MBP were isolated from normal rhesus monkeys using the same primary limiting dilution technique that is now widely used to generate human autoreactive T cell clones in vitro. Three different epitopes were recognized by three rhesus T cell lines isolated from three different monkeys. Upon activation, all lines produced interferon-gamma, interleukin-2, tumor necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor but neither interleukin-4 nor transforming growth factor-beta. The MBP-specific T cells were injected intravenously without adjuvant into the nonirradiated autologous monkey. One of the three rhesus monkeys developed an encephalomyelitis with a pleocytosis in the spinal fluid and perivascular infiltrates in the leptomeninges, spinal nerve roots and cerebral cortex. The data demonstrate that the normal immune repertoire of a primate species contains MBP-specific CD4+ T cells that are able to induce an autoimmune encephalomyelitis upon transfer into the nonirradiated autologous recipient.
authors.affiliation: Department of Neuroimmunology, Max-Planck Institute of Psychiatry, Martinsried, Germany.
authors.forename: E
authors.initials: E
authors.lastname: MeinL
authors.forename: R M
authors.initials: RM
authors.lastname: Hoch
authors.forename: K
authors.initials: K
authors.lastname: Dornmair
authors.forename: R
authors.initials: R
authors.lastname: de Waal Malefyt
authors.forename: R E
authors.initials: RE
authors.lastname: Bontrop
authors.forename: M
authors.initials: M
authors.lastname: Jonker
authors.forename: H
authors.initials: H
authors.lastname: Lassmann
authors.forename: R
authors.initials: R
authors.lastname: Hohlfeld
authors.forename: H
authors.initials: H
authors.lastname: Wekerle
authors.forename: B A
authors.initials: BA
authors.lastname: 't Hart
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology*; D002460:Cell Line; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D004679:Encephalomyelitis / Q000209:etiology*; D000939:Epitopes; D005260:Female; D008253:Macaca mulatta / Q000502:physiology*; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism*; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D000939:Epitopes; D004676:Myelin Basic Protein