Journal
JOURNAL OF AUTOIMMUNITY
Volume 32, Issue 2, Pages 125-132Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2009.01.004
Keywords
Apoptosis; Idiotopes; Multiple sclerosis; Oligodendrocytes; T cells
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Funding
- The Faculty of Medicine, University of Oslo
- The Odd Fellow Organization of Norway
- The Norwegian Foundation for Health and Rehabilitation
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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. (C) 2009 Elsevier Ltd. All rights reserved.
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