CXCL10 (IFN-gamma-inducible protein-10) control of encephalitogenic CD4(+)T cell accumulation in the central nervous system during experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) Th1-mediated de myelinating disease of the CNS that serves as a model for multiple sclerosi s. A critical event in the pathogenesis of EAE is the entry of both Ag-spec ific and Ag-nonspecific T lymphocytes into the CNS. In the present report, we investigated the role of the CXC chemokine CXCL10 (IFN-gamma -inducible protein-10) in the pathogenesis of EAE. Production of CXCL10 in the CNS cor related with the development of clinical disease. Administration of anti-CX CL10 decreased clinical and histological disease incidence, severity, as we ll as infiltration of mononuclear cells into the CNS. Anti-CXCL10 specifica lly decreased the accumulation of encephalitogenic PLP139-151 Ag-specific C D4(+) T cells in the CNS compared with control-treated animals. Anti-CXCL10 administration did not affect the activation of encephalitogenic T cells a s measured by Ag-specific proliferation and the ability to adoptively trans fer EAE. These results demonstrate an important role for the CXC chemokine CXCL10 in the recruitment and accumulation of inflammatory mononuclear cell s during the pathogenesis of EAE.