Encephalitogenic potential of myelin basic protein-specific T cells isolated from normal rhesus macaques.
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.
MeinL
E
E
Department of Neuroimmunology, Max-Planck Institute of Psychiatry, Martinsried, Germany.
Hoch
R M
RM
Dornmair
K
K
de Waal Malefyt
R
R
Bontrop
R E
RE
Jonker
M
M
Lassmann
H
H
Hohlfeld
R
R
Wekerle
H
H
't Hart
B A
BA
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*
D016207:Cytokines; D000939:Epitopes; D004676:Myelin Basic Protein