Diabetes acceleration or prevention by a coxsackievirus B4 infection: critical requirements for both interleukin-4 and gamma interferon
| Autor: | Tamir M. Ellis, Melissa A. Pierce, Michael S. Stalvey, Eric W. Ottendorfer, Martha Campbell-Thompson, Clive Wasserfall, Brian J. O'Donnell, James B. Flanagan, David V. Serreze, Charles J. Gauntt, Mark A. Atkinson |
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| Rok vydání: | 2004 |
| Předmět: |
Immunology
Nod Coxsackievirus Microbiology Pathogenesis Interferon-gamma Islets of Langerhans Mice Mice Inbred NOD Virology Diabetes mellitus medicine Enterovirus Infections Animals Interferon gamma Pancreas NOD mice Type 1 diabetes biology Pancreatic islets biology.organism_classification medicine.disease Enterovirus B Human medicine.anatomical_structure Diabetes Mellitus Type 1 Insect Science Pathogenesis and Immunity Female Interleukin-4 medicine.drug |
| Zdroj: | Journal of virology. 79(2) |
| ISSN: | 0022-538X |
| Popis: | Type 1 diabetes acceleration in nonobese diabetic (NOD) mice through coxsackievirus B4 (CVB4) infection requires a preexisting critical mass of autoreactive T cells in pancreatic islets, and in the absence of this insulitic threshold, CVB4 infection leads to long-term disease protection. To understand this acceleration and protection process, we challenged 8- and 12-week-old NOD mice containing a disruption in interleukin-4 (IL-4) or gamma interferon (IFN-γ) genes (NOD IL-4−/−and NOD IFN-γ−/−, respectively) with a diabetogenic, pancreatropic Edwards strain of CVB4. The elimination of IL-4 did not alter the rate of insulitis or diabetes development in NOD mice, while the elimination of IFN-γ delayed these events several weeks. CVB4 infection in 8-week-old mice only significantly accelerated the onset of diabetes in a subset of standard, but not IL-4- or IFN-γ-deficient, NOD mice. Long-term diabetes protection was established in standard NOD mice as well as in the NOD IFN-γ−/−mice that did not rapidly develop disease following CVB4 infection at 8 weeks of age. When mice were infected at 12 weeks of age, the onset of diabetes was accelerated in NOD IL-4−/−mice, while neither acceleration nor long-term protection was elicited in NOD IFN-γ−/−mice. No differences were observed in the kinetics of CVB4 clearance in pancreases from NOD, NOD IL-4−/−, and NOD IFN-γ−/−mice. Collectively, these results suggest that at the insulitis threshold at which CVB4 infection can first accelerate the onset of diabetes in NOD mice, IL-4 as well as IFN-γ contributes to this pathogenic process. The protective mechanism against diabetes elicited in NOD mice infected with CVB4 prior to the development of a critical threshold level of insulitis requires neither IL-4 nor IFN-γ. |
| Databáze: | OpenAIRE |
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