Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 116, Issue 5, Pages 1371-1381Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI27191
Keywords
-
Categories
Funding
- NIAID NIH HHS [AI51973, U19 AI051973] Funding Source: Medline
- NIDDK NIH HHS [R29 DK051091, R01 DK051091, DK51061, DK69872, R21 DK069872] Funding Source: Medline
Ask authors/readers for more resources
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-CD36-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 insuhn-specific Tregs producing IL-10, TGF-beta, and IL-4 was strongly enhanced. These ceRs 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available