Differential roles for CXCR3 in CD4+ and CD8+ T cell trafficking following viral infection of the CNS.
Lymphocyte infiltration into the central nervous system (CNS) following viral infection represents an important component of host defense and is required for control of viral replication. However, the mechanisms governing inflammation in response to viral infection of the CNS are not well understood. Following intracranial (i.c.) infection of susceptible mice with mouse hepatitis virus (MHV), mice develop an acute encephalomyelitis followed by a chronic demyelinating disease. The CXC chemokine ligand 10 (CXCL10) is expressed following MHV infection and signals T cells to migrate into the CNS. The functional contribution of the CXCL10 receptor CXCR3 in host defense and disease in response to MHV infection was evaluated. The majority of CD4+ and CD8+ T cells infiltrating the CNS following MHV infection express CXCR3. Administration of anti-CXCR3 antibody reduced CD4+ T cell infiltration (p<or=0.05), while CD8+ T cell trafficking was not affected. Anti-CXCR3 treatment during chronic disease correlated with improved motor skills and reduced demyelination. The selective effect of anti-CXCR3 treatment on CD4+ T cells was not the result of either reduced proliferation or modulation in chemokine receptor gene expression. Therefore, CXCR3 signaling has a non-redundant role in T cell subset trafficking in response to viral infection.
Stiles
Linda N
LN
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA.
Hosking
Martin P
MP
Edwards
Robert A
RA
Strieter
Robert M
RM
Lane
Thomas E
TE
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D020805:Central Nervous System Viral Diseases / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D004679:Encephalomyelitis / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D007249:Inflammation / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000276:immunology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology
D000911:Antibodies, Monoclonal; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine