title: Chemokine and matrix metalloproteinase secretion by myelin proteolipid protein-specific CD8+ T cells: potential roles in inflammation.
abstract: 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.
authors.affiliation: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Biddison
authors.forename: D D
authors.initials: DD
authors.lastname: Taub
authors.forename: W W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: D M
authors.initials: DM
authors.lastname: Center
authors.forename: E W
authors.initials: EW
authors.lastname: Connor
authors.forename: K
authors.initials: K
authors.lastname: Honma
mesh_terms: D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC; D017364:Collagenases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D019410:Interleukin-16 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D000939:Epitopes; D019410:Interleukin-16; D019402:Macrophage Inflammatory Proteins; D018991:Myelin Proteolipid Protein; D010455:Peptides; D017364:Collagenases; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9