HuFlt3‐L treatment does not protect RIP‐GP and RIP‐NP C57Bl/6 mice against LCMV‐induced diabetes.

Abstract

Human Fms‐like Tyrosine Kinase3‐L (huFlt3‐L) treatment of prediabetic NOD mice has been shown to increase the intrinsically low numbers of myeloid dendritic cells in these mice, while decreasing insulitis and delaying the progression of diabetes. In this study, we investigated the influence of huFlt3‐L treatment on insulitis and diabetes onset in the LCMV‐induced RIP‐GP (fast onset) or RIP‐NP (slow onset) C57Bl/6 mouse models of T1D. We showed that these mice have no intrinsic abnormality in DC subset development during LCMV infection. As expected, huFlt3‐L treatment dramatically increased the total DC fraction and numbers in both spleen and pancreatic draining LN, with a preferential outgrowth of myeloid DCs (CD11c+B220−CD11b+) over plasmacytoid DCs (CD11c+B220+CD11b−). Moreover, NK cells and NK‐DC cells were also increased, but CD4 and CD8 T cell fractions were reduced. Strikingly, repeated huFlt3‐L administrations, initiated in the prediabetic phase, did not protect against diabetes onset in this model. It is possible that this is correlated with the observed reduced fraction of CD4+CD25+ T cells in the huFlt3‐L‐treated mice. Translation of these data suggests that huFlt3‐L might only be a useful therapeutic agent for T1D patiens with a demonstrated DC (subset) defect.