Mucosal Gamma/Delta T Cells Increased by i.n. Administration of Gliadin to Four-Week-Old NOD Mice Prevent Diabetes in the NOD-SCID Model of Adoptive Cotransfer of Diabetes

Abstract

Beta-cell autoantigens, e.g., insulin, proinsulin, or GAD65, have been investigated both in animal models and human trials for induction of beta-cell specific tolerance to prevent the development of type 1 diabetes (T1D). On the other hand, environmental factors that significantly contribute to the recent outbreak of T1D were less studied, probably due to their complexity. The dietary wheat protein fraction has been associated with high penetrance of the disease, whereas gluten-free diets prevented T1D in animal models. We have previously reported that i.n. administration of gliadin prevented diabetes in NOD mice. Herewith we investigated mucosal gamma/delta T cells that were induced by i.n. administration of gliadin for their regulatory capacity to prevent diabetes in the NOD-SCID model of diabetes co-transfer. I.n. administration of gliadin to 4-week-old NOD mice increased proportion of gamma/delta T cells in pancreatic and mesenteric lymph nodes. Adoptive co-transfer of 2x106 gamma/delta T cells with 1x107 diabetogenic splenocytes led to statistically significant (p<0.01) diabetes prevention. The gamma/delta T cells were characterized for their memory-naïve and mucosal homing properties, or NK-like features by assessing expression of CD8alpha, CD45RB, CD62L, CCR7, CD103 and NKG2D by flowcytometry. In conclusion, similar to i.n. administration of insulin, i.n. vaccination with gliadin, an environmental antigen with possible ethiological influence in T1D, led to increased proportion of mucosal gamma/delta T cells. These gamma/delta T cells possess regulatory capacity to prevent diabetes transfer in the NOD-SCID model and may represent a novel and safer strategy for prevention or an early intervention in T1D. Disclosure D. Funda: None. J. Golias: None. M. Haupt-Jorgensen: None. K. Buschard: None.