| First Author | Bresson D | Year | 2006 |
| Journal | J Clin Invest | Volume | 116 |
| Issue | 5 | Pages | 1371-81 |
| PubMed ID | 16628253 | Mgi Jnum | J:108962 |
| Mgi Id | MGI:3625415 | Doi | 10.1172/JCI27191 |
| Citation | Bresson D, et al. (2006) Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. J Clin Invest 116(5):1371-81 |
| abstractText | Safe induction of autoantigen-specific long-term tolerance is the 'holy grail' for the treatment of autoimmune diseases. In animal models of type 1 diabetes, oral or i.n. immunization with islet antigens induces Tregs that are capable of bystander suppression. However, such interventions are only effective early in the prediabetic phase. Here, we demonstrate that a novel combination treatment with anti-CD3epsilon-specific antibody and i.n. proinsulin peptide can reverse recent-onset diabetes in 2 murine diabetes models with much higher efficacy than with monotherapy with anti-CD3 or antigen alone. In vivo, expansion of CD25(+)Foxp3(+) and insulin-specific Tregs producing IL-10, TGF-beta, and IL-4 was strongly enhanced. These cells could transfer dominant tolerance to immunocompetent recent-onset diabetic recipients and suppressed heterologous autoaggressive CD8 responses. Thus, combining a systemic immune modulator with antigen-specific Treg induction is more efficacious in reverting diabetes. Since Tregs act site-specifically, this strategy should also be expected to reduce the potential for systemic side effects. |
