| First Author | Richer MJ | Year | 2008 |
| Journal | Diabetes | Volume | 57 |
| Issue | 5 | Pages | 1302-11 |
| PubMed ID | 18268045 | Mgi Jnum | J:135251 |
| Mgi Id | MGI:3790908 | Doi | 10.2337/db07-1460 |
| Citation | Richer MJ, et al. (2008) Regulatory T-cells protect from type 1 diabetes after induction by coxsackievirus infection in the context of transforming growth factor-beta. Diabetes 57(5):1302-11 |
| abstractText | OBJECTIVE: Coxsackievirus infections have long been associated with the induction of type 1 diabetes. Infection with coxsackievirus B4 (CB4) enhances type 1 diabetes onset in NOD mice by accelerating the presentation of beta-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 type 1 diabetes onset in NOD mice. This defect may contribute to susceptibility to viral-induced type 1 diabetes. We asked whether the immune response after CB4 infection could be manipulated to reestablish peripheral tolerance while maintaining the immune response to virus. RESEARCH DESIGN AND METHODS: NOD mice expressing transforming growth factor-beta (TGF-beta) specifically in the beta-cells were infected with CB4, and the functional role of Tregs in disease protection was measured. Systemic treatments with TGF-beta were used to assess its therapeutic potential. RESULTS: Here, we report that Tregs induced after CB4 infection in the presence of TGF-beta prevented type 1 diabetes. The capacity to directly infect pancreatic beta-cells correlated with increased numbers of pancreatic Tregs, suggesting that presentation of beta-cell antigen is integral to induction of diabetogenic protective Tregs. Furthermore, the presence of these viral induced Tregs correlated with protection from type 1 diabetes without altering the antiviral response. Finally, when TGF-beta was administered systemically to NOD mice after infection, the incidence of type 1 diabetes was reduced, thereby signifying a potential therapeutic role for TGF-beta. CONCLUSIONS: We demonstrate manipulations of the immune response that result in Treg-mediated protection from type 1 diabetes without concomitant loss of the capacity to control viral infection. |
