| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
Programs in
*
Immunology and Virology and
Molecular Medicine and Departments of
Medicine and
Pathology, University of Massachusetts Medical School, Worcester, MA 01655; and
¶ Division of Cell Biology, Section of Immunology, Faculty of Medical Sciences, University of Groningen, Groningen, The Netherlands
Viruses are believed to contribute to the pathogenesis of autoimmune type 1A diabetes in humans. This pathogenic process can be modeled in the BBDR rat, which develops pancreatic insulitis and type 1A-like diabetes after infection with Kilham’s rat virus (RV). The mechanism is unknown, but does not involve infection of the pancreatic islets. We first documented that RV infection of BBDR rats induces diabetes, whereas infection with its close homologue H-1 does not. Both viruses induced similar humoral and cellular immune responses in the host, but only RV also caused a decrease in splenic CD4+CD25+ T cells in both BBDR rats and normal WF rats. Surprisingly, RV infection increased CD4+CD25+ T cells in pancreatic lymph nodes of BBDR but not WF rats. This increase appeared to be due to the accumulation of nonproliferating CD4+CD25+ T cells. The results imply that the reduction in splenic CD4+CD25+ cells observed in RV-infected animals is virus specific, whereas the increase in pancreatic lymph node CD4+CD25+ cells is both virus and rat strain specific. The data suggest that RV but not H-1 infection alters T cell regulation in BBDR rats and permits the expression of autoimmune diabetes. More generally, the results suggest a mechanism that could link an underlying genetic predisposition to environmental perturbation and transform a "regulated predisposition" into autoimmune diabetes, namely, failure to maintain regulatory CD4+CD25+ T cell function.
This article has been cited by other articles:
|
|
 |
|
  E. P. Blankenhorn, L. Cort, D. L. Greiner, D. L. Guberski, and J. P. Mordes Virus-Induced Autoimmune Diabetes in the LEW.1WR1 Rat Requires Iddm14 and a Genetic Locus Proximal to the Major Histocompatibility Complex Diabetes, December 1, 2009; 58(12): 2930 - 2938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. CHOPRA, P. DIIORIO, S. C. PINO, S. B. WILSON, N. E. PHILLIPS, J. P. MORDES, A. A. ROSSINI, D. L. GREINER, L. D. SHULTZ, and R. BORTELL Failure of {alpha}-Galactosylceramide to Prevent Diabetes in Virus-inducible Models of Type 1 Diabetes in the Rat In Vivo, March 1, 2009; 23(2): 195 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Smith, S. Efstathiou, and A. Cooke Murine Gammaherpesvirus-68 Infection Alters Self-Antigen Presentation and Type 1 Diabetes Onset in NOD Mice J. Immunol., December 1, 2007; 179(11): 7325 - 7333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Neu, M. Douglas-Escobar, and M. Lopez Microbes and the Developing Gastrointestinal Tract Nutr Clin Pract, April 1, 2007; 22(2): 174 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zipris, E. Lien, A. Nair, J. X. Xie, D. L. Greiner, J. P. Mordes, and A. A. Rossini TLR9-Signaling Pathways Are Involved in Kilham Rat Virus-Induced Autoimmune Diabetes in the Biobreeding Diabetes-Resistant Rat J. Immunol., January 15, 2007; 178(2): 693 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Geoffrey, S. Jia, A. E. Kwitek, J. Woodliff, S. Ghosh, A. Lernmark, X. Wang, and M. J. Hessner Evidence of a Functional Role for Mast Cells in the Development of Type 1 Diabetes Mellitus in the BioBreeding Rat J. Immunol., November 15, 2006; 177(10): 7275 - 7286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lundsgaard, T. L. Holm, L. Hornum, and H. Markholst In Vivo Control of Diabetogenic T-Cells by Regulatory CD4+CD25+ T-Cells Expressing Foxp3 Diabetes, April 1, 2005; 54(4): 1040 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. Blankenhorn, L. Rodemich, C. Martin-Fernandez, J. Leif, D. L. Greiner, and J. P. Mordes The Rat Diabetes Susceptibility Locus Iddm4 and at Least One Additional Gene Are Required for Autoimmune Diabetes Induced by Viral Infection Diabetes, April 1, 2005; 54(4): 1233 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zipris, E. Lien, J. X. Xie, D. L. Greiner, J. P. Mordes, and A. A. Rossini TLR Activation Synergizes with Kilham Rat Virus Infection to Induce Diabetes in BBDR Rats J. Immunol., January 1, 2005; 174(1): 131 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Hessner, X. Wang, L. Meyer, R. Geoffrey, S. Jia, J. Fuller, A. Lernmark, and S. Ghosh Involvement of Eotaxin, Eosinophils, and Pancreatic Predisposition in Development of Type 1 Diabetes Mellitus in the BioBreeding Rat J. Immunol., December 1, 2004; 173(11): 6993 - 7002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. I. Mendez, Y.-H. Chung, H.-S. Jun, and J.-W. Yoon Immunoregulatory Role of Nitric Oxide in Kilham Rat Virus-Induced Autoimmune Diabetes in DR-BB Rats J. Immunol., July 15, 2004; 173(2): 1327 - 1335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wen, J. Peng, Z. Li, and F. S. Wong The Effect of Innate Immunity on Autoimmune Diabetes and the Expression of Toll-Like Receptors on Pancreatic Islets J. Immunol., March 1, 2004; 172(5): 3173 - 3180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Rossini Autoimmune Diabetes and the Circle of Tolerance Diabetes, February 1, 2004; 53(2): 267 - 275. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
