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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | O'Connor, Richard A. Leech, Melanie D. Turner, Darryl G. Brown, Sheila Mellanby, Richard J. Gray, David Barr, Tom A. Anderton, Stephen M. |
| Description | Country affiliation: United kingdom Author Affiliation: Leech MD ( Medical Research Council Centre for Inflammation Research, Centre for Multiple Sclerosis Research and Centre for Immunity, Infection, and Evolution, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.) |
| Abstract | Mice lacking IL-6 are resistant to autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE), which is driven by CNS-reactive CD4(+) T cells. There are multiple cellular sources of IL-6, but the critical source in EAE has been uncertain. Using cell-specific IL-6 deficiency in models of EAE induced by active immunization, passive transfer, T cell transfer, and dendritic cell transfer, we show that neither the pathogenic T cells nor CNS-resident cells are required to produce IL-6. Instead, the requirement for IL-6 was restricted to the early stages of T cell activation and was entirely controlled by dendritic cell-derived IL-6. This reflected the loss of IL-6R expression by T cells over time. These data explain why blockade of IL-6R only achieves protection against EAE if used at the time of T cell priming. The implications for therapeutic manipulation of IL-6 signaling in human T cell-driven autoimmune conditions are considered. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1202925 |
| Journal | The Journal of Immunology |
| Issue Number | 3 |
| Volume Number | 190 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2013-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Dendritic Cells Immunology Encephalomyelitis, Autoimmune, Experimental Interleukin-6 Adoptive Transfer Animals Autoantigens Cd4-positive T-lymphocytes Transplantation Crosses, Genetic Secretion Histocompatibility Antigens Class Ii Immunization, Passive Deficiency Lymphocyte Activation Lymphokines Mice Mice, Inbred C57bl Mice, Knockout Myelin Basic Protein Myelin-oligodendrocyte Glycoprotein Peptide Fragments Receptors, Interleukin-6 Biosynthesis Specific Pathogen-free Organisms T-cell Antigen Receptor Specificity Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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