Among CXCR3 chemokines, IFN-gamma-inducible protein of 10 kDa (CXC chemokine ligand (CXCL) 10) but not monokine induced by IFN-gamma (CXCL9) imprints a pattern for the subsequent development of autoimmune disease.
Infection of the pancreas with lymphocytic choriomeningitis virus results in rapid and differential expression among CXCR3 chemokines. IFN-gamma-inducible protein of 10 kDa (IP-10), in contrast with monokine induced by IFN-gamma and IFN-inducible T cell-alpha chemoattractant, is strongly expressed within 24 h postinfection. Blocking of IP-10, but not monokine induced by IFN-gamma, aborts severity of Ag-specific injury of pancreatic beta cells and abrogates type 1 diabetes. Mechanistically, IP-10 blockade impedes the expansion of peripheral Ag-specific T cells and hinders their migration into the pancreas. IP-10 expression was restricted to viruses infecting the pancreas and that are capable of causing diabetes. Hence, virus-induced organ-specific autoimmune diseases may be dependent on virus tropism and its ability to alter the local milieu by selectively inducing chemokines that prepare the infected tissue for the subsequent destruction by the adaptive immune response.
Christen
Urs
U
Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. christen@liai.org
McGavern
Dorian B
DB
Luster
Andrew D
AD
von Herrath
Matthias G
MG
Oldstone
Michael B A
MB
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018188:Cardiovirus Infections / Q000235:genetics / Q000276:immunology; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D004769:Enterovirus Infections / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007328:Insulin / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology / Q000378:metabolism / Q000821:virology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D018984:Epitopes, T-Lymphocyte; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma