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ORIGINAL ARTICLE

Effect of Modified Diabetic Splenocytes on Mice Injected with Multiple Low-Dose Streptozotocin

Centro de Investigaciones Endocrinológicas, CONICET, Hospital de Niños ``Ricardo Gutierrez'', Gallo 1360 (1425), Buenos Aires, Argentina

This work reports the effects of a previous injection of mitomycin-modified splenocytes from multiple-low dose streptozotocin-treated mice (mld-sz) on autoimmune diabetes produced by mld-sz. Our work shows that a previous inoculation of modified mononuclear splenocytes from mld-sz mice prevents alterations in glycemia, in insulin secretion (IS) pattern from isolated perifused islets, and in mass of pancreatic islets. Immunohistochemistry showed an alteration in the number of beta, but not of alpha or delta cells. While a mononuclear intra-islet infiltration was observed in mld-sz mice, a predominantly polar or peri-islet infiltration was seen in vaccinated mice. Islet-associated mononuclear cells from mld-sz mice produced diabetes and induced a diminished IS when transferred to normal receptors. Those cells from previously vaccinated mld-sz mice had no effect when injected into normal receptors. In addition, they also inhibited the damage induced in normal receptors by the islet-associated mononuclear cells from mld-sz animals. Cellular death was also prevented by previous vaccination. Our results suggest that vaccination with modified splenocytes from mld-sz mice is capable of shifting the islet cells infiltration pattern from an aggressive one toward a protective one and thus preventing the ß cell destruction observed in mld-sz mice.

Key Words: diabetes prevention • diabetes immunomodulation: vaccination • insulin secretion pattern • morphometric, Immunohistochemistry, and cellular death studies • Islet-associated mononuclear cell transfer

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