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.

Cerebrospinal fluid T cell clones from patients with multiple sclerosis: recognition of idiotopes on monoclonal IgG secreted by autologous cerebrospinal fluid B cells.

Due to somatic recombination and hypermutation, Ig variable heavy (V(H)) and light (V(L)) regions contain unique immunogenic determinants, idiotopes (Id), which can stimulate T cells. To address the relevance of this in a human disease, monoclonal IgG (mAb)-secreting B cell clones were established from the cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS). HLA-DR-restricted CD4(+) T cell lines and clones from CSF of both patients specifically recognized autologous CSF mAb.