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ORIGINAL ARTICLE

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

Centro de Investigaciones Endocrinológicas, Hospital de Niños Ricardo Gutiérrez, Gallo 1360, (1425), Buenos Aires, Argentina

Etiological agents of autoimmune processes that have been made nonvirulent by several treatments, i.e., mitomycin C (Mit C), can be used as a vaccine to protect against disease. In this work we studied the effects of splenocytes from diabetic mice on animals that had been injected with modified splenocytes (Mit C-treated splenocytes from multiple low-dose streptozotocin [mld-sz] mice) 15 days before. Splenocytes from mld-sz diabetic donors altered i.p. glucose tolerance and the first peak of insulin secretion pattern when injected into normal singeneic recipients. These effects can be prevented partially (one injection in a vaccine form) or completely (two injections with a 15-day interval) by a previous injection of Mit C-treated mononuclear splenocytes (MS) from mld-sz mice. The fact that control splenocytes previously treated with Mit C were not able to achieve similar results indicates that donor splenocytes have to be diabetic to prevent the disease. On the other hand, Mit C-treated diabetic MS were not effective in preventing the alterations in glucose tolerance and in the pattern of insulin secretion when injected into athymic mice. This suggests that the preventive effect of Mit C-treated diabetic MS injection also implies an active role of the T cells from the recipient mice. Mit C-treated diabetic splenocytes are preferentially trapped by the pancreas and the lymph nodes from recipient mice. Our results show that the impairment in glucose tolerance and in the insulin secretion pattern produced by diabetic splenocyte transfer can be prevented by one or two previous injections of Mit C-modified diabetic splenocytes.

Key Words: diabetic prevention • diabetes immunomodulation • vaccination • mononuclear cell transfer • insulin secretion patterns