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 demyelinating disease of the CNS that serves as a model for multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific 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 correlated with the development of clinical disease. Administration of anti-CXCL10 decreased clinical and histological disease incidence, severity, as well as infiltration of mononuclear cells into the CNS. Anti-CXCL10 specifically decreased the accumulation of encephalitogenic PLP(139-151) Ag-specific CD4+ T cells in the CNS compared with control-treated animals. Anti-CXCL10 administration did not affect the activation of encephalitogenic T cells as measured by Ag-specific proliferation and the ability to adoptively transfer EAE. These results demonstrate an important role for the CXC chemokine CXCL10 in the recruitment and accumulation of inflammatory mononuclear cells during the pathogenesis of EAE.
Fife
B T
BT
Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, and Institute for Neuroscience, Northwestern University Medical School, Chicago, IL 60611, USA.
Kennedy
K J
KJ
Paniagua
M C
MC
Lukacs
N W
NW
Kunkel
S L
SL
Luster
A D
AD
Karpus
W J
WJ
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage; D007156:Immunologic Memory; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D007106:Immune Sera; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine