Damien Bresson, Yulia Manenkova and Matthias von Herrath (Principal Investigator)
Several studies described the expression the OX40 (CD134) co-receptor (a member of the TNF/TNFR family) at the surface of regulatory T cells (Tregs) in mice but also in humans. Previous studies have shown the involvement of this pathway in controlling some aspects of the induction, expansion and survival of Tregs in vivo. However, it is still unclear whether expression of the OX40 molecule at the surface of Tregs is involved and/or necessary to mediate their suppressive function in vivo. We obtained OX40-deficient (OX40-/-) animals from Mick Croft's laboratory that we crossed to a virally-induced model for type 1 diabetes (T1D) also known as RIP-LCMV-GP mice. We recently showed in this animal model that GAD65-specific Tregs are able mediate protection from T1D when transferred into immuno-competent RIP-LCMV-GP mice. We would like to address the question of whether the bystander suppressive effect is mediated in both OX40-sufficient or -deficient GAD65-specific Tregs in vivo. These data could be important to better understand the function of OX40 expressed at the surface of Tregs and in particular to define whether expression of OX40 molecule on antigen-specific Tregs is necessary for their suppressive function in vivo. Therapeutically, infusion of Tregs is now being envisioned to treat T1D (or other autoimmune diseases). In this setting, infusion of Tregs expressing or not OX40 could have distinct therapeutic efficacies in human clinical trials.