CD8(-SPECIFIC T-CELLS CAN CHEMOATTRACT CD4(+) MYELIN PEPTIDE-SPECIFICT-CELLS - IMPORTANCE OF IFN-INDUCIBLE PROTEIN-10() MYELIN PEPTIDE)

The demyelination process that occurs in the central nervous system (C NS) of patients with multiple sclerosis (MS) is due, in part, to an in flammatory response in which CD4(+) and CD8(+) T cells and macrophages infiltrate white matter, While it is thought that the inflammatory an d demyelination process in MS is the product of Th1-associated cytokin es secreted by CD4(+) myelin protein-specific T cells present in the C NS, the mechanisms that are responsible for the recruitment and mainte nance of these myelin-reactive CD4(+) T cells in the CNS have not been elucidated, We have shown previously that CD8(+)CTL that recognize pe ptides derived from sequences of the myelin proteolipid protein (PLP) presented by HLA class I molecules can be generated in vitro, and that these PLP-specific CD8(+)CTL secrete the proinflammatory chemokines m acrophage-inflammatory protein-1 alpha and -1 beta, IL-16, and IP-10. In this study, we demonstrate that soluble products of these PLP-speci fic CD8(+)CTL can chemoattract CD4(+) T cells that are specific for a myelin basic protein peptide and a PLP peptide, and that the majority of this chemotactic activity is mediated by IFN-inducible protein 10. These results demonstrate that PLP-specific CD8(+) T cells can play a role in the recruitment and retention of myelin-derived peptide-specif ic CD4(+) T cells, and indicate that they may play a proinflammatory r ole in the pathogenesis of MS.