Idiotope-specific CD4(+) T cells induce apoptosis of human oligodendrocytes.
CD4(+) T cells specific for immunologic non-self determinants on self-IgG, idiotopes (Id), can be raised from cerebrospinal fluid (CSF) and blood of patients with multiple sclerosis (MS). To test if Id-specific CD4(+) T cells have the potential to destroy oligodendrocytes (ODCs), we analyzed their ability to induce apoptosis of human ODC cell lines. Id-specific CD4(+) T cells stimulated with either Id-bearing B cells, Id-peptide presented by other antigen presenting cells, or by anti-CD3/anti-CD28 in the absence of accessory cells induced DNA fragmentation and killed ODCs. Killing required contact between the ODCs and the T cells, it did not depend on the cytokine profile of the T cells, it was independent of other cell types, and was inhibited by a general caspase inhibitor and an anti-Fas antibody. Activated CD4(+) T cells specific for glutamic acid decarboxylase 65 also induced apoptosis, showing that killing does not depend on cognate interaction between T cells and target cells but rather on the activation status of the T cells.
Hestvik
Anne Lise Karlsgot
AL
Institute of Immunology, Faculty of Medicine, University of Oslo, Oslo University Hospital Rikshospitalet, Oslo, Norway. anne.lise.hestvik@rr-research.no
Skorstad
Gjertrud
G
Vartdal
Frode
F
Holmøy
Trygve
T
D000328:Adult; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D020169:Caspases / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D009836:Oligodendroglia / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
D000906:Antibodies; D019014:fas Receptor; D020169:Caspases