The
demyelination process that occurs in the central nervous system of patients with
multiple sclerosis (MS) is, in part, due to an inflammatory response in which CD4+ and CD8+ T cells and macrophages infiltrate white matter. Although many studies have characterized
myelin protein-specific CD4+ T cells, we have demonstrated that CD8+ CTL specific for myelin
peptides can be identified. In the present study, the potential roles of these CD8+ CTL in the generation of the inflammatory responses associated with MS have been investigated by measuring the capacity of these T cells to secrete the following proinflammatory
chemokines: macrophage inflammatory protein-1alpha (MIP-1alpha) and
MIP-1beta,
lymphocyte chemoattractant factor (IL-16), IFN-inducible protein-10, as well as the proinflammatory
enzymes of the
matrix metalloproteinase family. The CD8+ CTL lines tested are derived from MS patients and are specific for two different
myelin proteolipid protein-derived
peptides presented by
HLA-A2 and
HLA-A3. All of the 17 CD8+ CTL lines secreted detectable amounts of
MIP-1alpha and
MIP-1beta. Nine of twelve CTL lines tested secreted
IL-16, 10 of 12 lines tested secreted IFN-inducible protein-10, and 14 of 16 lines tested secreted
matrix metalloproteinase-9. Collectively, these results indicate that
myelin proteolipid protein peptide-specific CD8+ CTL may be an important source of proinflammatory soluble mediators that could promote and mediate the inflammatory response in MS
demyelination.