Flt3L-derived Antigen Presenting Cell transfer in neonatal NOD mice delays the incidence of Type 1

<p dir="ltr">Type 1 Diabetes (T1D) is an autoimmune disease characterized by progressive stages culminating in T cell mediated destruction of the b cells at the islets of Langerhans. The immune mechanisms that initiate T1D are not fully resolved but likely involve interaction between pro-inflammatory antigen presenting cells and autoreactive T cells that initiate immune infiltration and activation. Previous studies have tested the use of tolerogenic antigen presenting cells (APCs) in adult non-obese-diabetic (NOD) female mice to delay or prevent T1D with only slight to intermediate success. Moreover, immune infiltration begins as early as 4 weeks old, therefore targeting autoreactive T cells with tolerogenic APCs in adult mice may not impact late stages of diabetes. Thus, we hypothesize that the transfer of tolerogenic APCs at the neonatal stage prior to priming and immune infiltration will result in effective protection from autoimmunity. Our studies demonstrate that immature APCs travel to the pancreatic draining lymph nodes, alter the cytokine milieu in young mice, divert autoreactive CD4⁺ T cells to anergy and drastically decrease proliferation and function of CTLs in adult pre-diabetic mice leading to a significant reduction in the incidence of T1D.</p>