HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix Figures All Versions of this Article: db07-1460v1 57/5/1302    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Richer, M. J. Articles by Horwitz, M. S. Search for Related Content PubMed PubMed Citation Articles by Richer, M. J. Articles by Horwitz, M. S. Social Bookmarking                What's this?

Regulatory T cells protect from type 1 diabetes following induction by coxsackievirus infection in the context of TGF-β.

¹Microbiology and Immunology, The University of British Columbia, 3551-2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3

Objective: Coxsackievirus infections have long been associated with the induction of type 1 diabetes (T1D). Infection with coxsackievirus B4 (CB4) enhances T1D onset in non-obese diabetic (NOD) mice by accelerating the presentation of β cell antigen to autoreactive T cells. It has been reported that a progressive defect in regulatory T cell (Treg) function is, in part, responsible for T1D onset in NOD mice. This defect may contribute to susceptibility to viral-induced T1D. We asked whether the immune response following CB4 infection could be manipulated in order to re-establish peripheral tolerance while maintaining the immune response to virus.

Research Design and Methods: NOD mice expressing TGF-β specifically in the β cells were infected with CB4 and the functional role of Tregs in disease protection was measured. Systemic treatments with TGF-β were used to assess its therapeutic potential.

Results: Here, we report that Tregs induced following CB4 infection in the presence of TGF-β prevented T1D. Interestingly, the capacity to directly infect pancreatic β cells correlated with increased numbers of pancreatic Tregs suggesting that presentation of β cell antigen is integral to induction of diabetogenic protective Tregs. Furthermore, the presence of these viral induced Tregs correlated with protection from T1D without altering the anti-viral response. Finally, when TGF-β was administered systemically to NOD mice post-infection the incidence of T1D was reduced thereby signifying a potential therapeutic role for TGF-β.

Conclusions: We demonstrate manipulations of the immune response that result in Treg-mediated protection from T1D without concomitant loss of the capacity to control viral infection.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. M. Filippi, A. E. Juedes, J. E. Oldham, E. Ling, L. Togher, Y. Peng, R. A. Flavell, and M. G. von Herrath Transforming Growth Factor-{beta} Suppresses the Activation of CD8+ T-Cells When Naive but Promotes Their Survival and Function Once Antigen Experienced: A Two-Faced Impact on Autoimmunity Diabetes, October 1, 2008; 57(10): 2684 - 2692. [Abstract] [Full Text] [PDF]