EXPRESSION OF CHEMOKINE GENES IN RAT GLIAL-CELLS - THE EFFECT OF MYELIN BASIC PROTEIN-REACTIVE ENCEPHALITOGENIC T-CELLS

Chemokine gene expression and chemokine activity appear to be major co mponents of the immunopathological processes of inflammation and autoi mmunity, To initiate an investigation of the role of chemokines in the pathogenesis of autoimmune inflammatory demyelination, we examined th e expression of mRNA transcripts encoding four prominent chemokines, I P-10, MIP-1 alpha, MCP-1, and RANTES, in encephalitogenic rat MBP-reac tive T cells, astrocytes, and microglia, Astrocytes and microglia, whe ther as lines or as freshly isolated cells, did not constitutively exp ress IP-10 and MCP-1 mRNA but could be induced with LPS to also produc e MIP-1 alpha and RANTES, MBP-reactive T cells were induced,vith MBP t o produce abundant levels of MIP-1 alpha, MCP-1, and RANTES mRNA in di fferent temporal profiles but did not express IP-10 mRNA, In an MHC-II restricted fashion, the antigen-activated MBP-reactive T cells also i nduced glial cells to express all four chemokines, with the chemokine gene expression greatest following T-cell interactions with MHC-compat ible glia. Treatment of glial cells with TNF-alpha and IFN-gamma induc ed only IP-10, indicating that the expression of chemokine genes other than IP-10 requires a combination of different cytokines or direct ce ll-cell contact between T cells and glia, Quantitative assays revealed that activated astrocytes, the dominant glia of the CNS, express high er levels of chemokine transcripts than transcripts of the major proin flammatory cytokines TNF-alpha and IFN-gamma. These results underscore the prominent but complex expression of chemokines by cellular compon ent of inflammatory demyelinating lesions. (C) 1997 Wiley-Liss, Inc.