This study describes the morphology, time appearance, persistence, and
immunomodulation of extraislet infiltration in the nonobese diabetic
(NOD) mouse pancreas. Female NOD mice were subdivided into two groups:
untreated, killed at week 5 (n = 8), 10 (n = 8), or 21 (n = 8) of lif
e; ganglioside treated (200 mg/kg body wt/day given from week 4 until
week 21 of life, plus complete Freund's adjuvant at week 4), killed at
week 10 (n = 6), 21 (n = 6), or 25 (4 weeks after the end of the gang
lioside treatment; n = 6). Mononuclear elements were seen around small
ductules located both in the vicinity of and far from the islets. Lar
ger ducts were completely devoid of inflammation, thus evidencing that
periductulitis is specific only to small ductules. Moreover, an exocr
ine focal pancreatitis was seen along septa and may demonstrate that m
acrophage activation takes place throughout the pancreatic connective
tissue. Immunomodulation determines some suppression of insulitis; nev
ertheless, after treatment withdrawal, a reinfiltration occurs both wi
thin and outside the islets.