Detection of dendritic cells in the non-obese diabetic (NOD) mouse islet pancreas infiltrate is correlated with Th2-cytokine production

Abstract

We investigate the role played by dendritic cells (DCs) in the non-obese diabetic (NOD) mouse pancreas. The early peri-islet, nondestructive infiltration phase, and intra-islet, destructive infiltration phase, which immediately precedes overt diabetes, are studied. Results show that infiltrating cells are Ia-b, ICAM-1, and, mainly, MIDC-8 immunoreactive (ir). These data from silica-treated animals and ultrastructural observations strongly support the hypothesis that DCs are both Ia-b-ir and ICAM-1-ir and that they exert a pivotal role during the period of early infiltration. This is a novel finding for NOD mice and increases the interest for this protective cell type during the rather complex islet infiltration process. Moreover, the cytokine profile demonstrates that Th2 protective cytokines are specific for peri-islet infiltrate. Disappearance of DCs from the infiltrate is concomitant with both the formation of intra-islet infiltration and the increase in proinflammatory Th1 cytokine levels. This further supports the hypothesis that DCs may exert a protective role against diabetes development.

Immunomodulation of autoimmune diabetes by dendritic cells

“…Papaccio et al [26] reported the disappearance of DCs from peri-islet infiltrate coincided with an increase in systemic proinflammatory Th1 cytokine levels. Using the RIP-mOVA transgenic mouse model, Kurts et al [27] have shown that OT-I cells activated by cross-presentation are subsequently deleted from the peripheral pool of recirculating lymphocytes, a process for deletion of antigen-specific CD8 + T cells that depended on DCs with exquisite tolerogenic properties [27].…”