Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Blocking / administration & dosage
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Antibodies, Monoclonal / administration & dosage
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / pathology
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Cardiovirus Infections / genetics
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Cardiovirus Infections / immunology
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Cell Migration Inhibition
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Cell Movement / genetics
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Cell Movement / immunology
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Chemokine CXCL10
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Chemokine CXCL9
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Chemokines, CXC / antagonists & inhibitors
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Chemokines, CXC / biosynthesis*
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Chemokines, CXC / immunology
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Chemokines, CXC / physiology
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Diabetes Mellitus, Type 1 / genetics
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Diabetes Mellitus, Type 1 / immunology*
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Diabetes Mellitus, Type 1 / pathology
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Diabetes Mellitus, Type 1 / prevention & control
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Enterovirus Infections / genetics
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Enterovirus Infections / immunology
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Epitopes, T-Lymphocyte / immunology
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Insulin / biosynthesis
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Intercellular Signaling Peptides and Proteins / biosynthesis*
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Intercellular Signaling Peptides and Proteins / immunology
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Intercellular Signaling Peptides and Proteins / physiology
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Interferon-gamma / physiology*
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Islets of Langerhans / immunology
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Islets of Langerhans / metabolism
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Islets of Langerhans / pathology
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Lymphocytic Choriomeningitis / genetics
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Lymphocytic Choriomeningitis / immunology
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Lymphocytic Choriomeningitis / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Pancreas / immunology
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Pancreas / metabolism
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Pancreas / virology
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Receptors, CXCR3
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Receptors, Chemokine / antagonists & inhibitors
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Receptors, Chemokine / biosynthesis*
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Receptors, Chemokine / immunology
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Receptors, Chemokine / physiology
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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CXCL9 protein, human
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CXCR3 protein, human
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Chemokine CXCL10
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Chemokine CXCL9
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Chemokines, CXC
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Cxcr3 protein, mouse
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Epitopes, T-Lymphocyte
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Insulin
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Intercellular Signaling Peptides and Proteins
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Receptors, CXCR3
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Receptors, Chemokine
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Interferon-gamma