Today's K-12 teachers are educating millennial students who are surrounded by the influences of technology, most of which has become increasingly mobile. Not only are students and teachers exposed to the influx of information that the Internet provides via at-home computers, but mobile devices have now made it possible to have access to up to date information anytime, anywhere. "Millennial" students are not only attuned to having on demand information available at their fingertips, but they expect it. This expectation prevails in the educational environment.

Co-stimulation serves as a critical checkpoint for T cell development and activation, and several genetic variants affecting co-stimulatory pathways confer risk for autoimmune diseases. A single nucleotide polymorphism in CD226 (rs763361; G307S) has been shown to increase susceptibility to type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. CD226 competes with the co-inhibitory receptor TIGIT (T cell immunoreceptor with Ig and ITIM domains) to bind CD155 to amplify TCR signaling. We previously found that Cd226 knockout protected non-obese diabetic (NOD) mice from disease, but the impact of CD226 signaling on individual immune subsets remained unclear. We focused on regulatory T cells (Tregs) as a population of interest, as prior reports demonstrated that human CD226+ Tregs exhibit reduced FOXP3+Helios+ purity and suppressive function following expansion. Hence, we hypothesized that global deletion of Cd226 would increase Treg stability and accordingly, Treg-specific Cd226 deletion would inhibit diabetes in NOD mice. Indeed, crossing the NOD.Cd226-/- and NOD.Foxp3-GFP-Cre.R26-loxP-STOP-loxP-YFP Treg-fate tracking strains resulted in increased Treg induction and decreased FoxP3-deficient ex-Tregs in the pancreatic lymph nodes. We generated a Treg-conditional knockout (Treg-deltaCd226) strain and found that female Treg-deltaCd226 mice had decreased insulitis and diabetes incidence compared to Treg-WT mice. Additionally, we observed increased TIGIT expression on Tregs and conventional CD4+ T cells within the pancreas of Treg-deltaCd226 versus Treg-WT mice. These findings demonstrate that an imbalance of CD226/TIGIT signaling may contribute to Treg destabilization in the NOD mouse and highlight the potential for therapeutic targeting of this pathway to prevent or reverse autoimmunity.