Adenovirus-mediated expression of CXCL10 in the central nervous system results in T-cell recruitment and limited neuropathology.
In the present study, the authors evaluated the contributions of the CXC chemokine ligand (CXCL)10 to leukocyte recruitment into the central nervous system (CNS) and disease development. Instillation of a replication-deficient adenovirus that expresses CXCL10 (AdCXCL10) into the CNS of C57BL/6 mice resulted in a rapid (day 3) and prolonged (day 21) infiltration of both CD4(+) and CD8(+) T cells as compared to mice infected with an adenovirus vector containing beta-galactosidase (Adbetagal). Despite increased T-cell infiltration into the CNS of AdCXCL10-infected mice, production of proinflammatory chemokines normally associated with the recruitment of activated T cells into the CNS was muted and mice developed limited neuropathology. Therefore, these results indicate that T-cell infiltration in the absence of appropriate activation is not sufficient to induce pathology within the CNS and that additional signals other than CXCL10 are required for induction of an immune-mediated neurologic disease.
Trifilo
Matthew J
MJ
Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900, USA.
Lane
Thomas E
TE
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001921:Brain; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D003673:Defective Viruses / Q000235:genetics*; D003711:Demyelinating Diseases / Q000209:etiology; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology; D005822:Genetic Vectors / Q000235:genetics*; D007267:Injections; D007763:Lac Operon; D008297:Male; D008581:Meningitis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000209:etiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014158:Transcription, Genetic
D054357:Chemokine CXCL10; D019743:Chemokines, CXC