ADMINISTRATION OF IL-4 PREVENTS AUTOIMMUNE DIABETES BUT ENHANCES PANCREATIC INSULITIS IN NOD MICE

The present study demonstrated that the administration of recombinant interleukin-4 (rIL-4) prevented overt diabetes in nonobese diabetic (N OD) mice whose T cells produced relatively low amounts of IL-4. Howeve r, massive insulitis was observed in rIL-4-treated NOD mice. The flow cytometric analysis of islet-infiltrating T cells revealed that the nu mber of CD45RB(low)CD4(+) T cells was significantly increased by in vi vo administration of rIL-4. By measuring the cytokine production of sp lenic T cells after stimulation, it was shown that CD45RB(low)CD4(+) T cells predominantly produced IL-4 and IL-10 but produced less IL-2 an d interferon-gamma (IFN-gamma). A semiquantitative reverse-transcripta se polymerase chain reaction assay revealed a higher expression of IL- 4 and IL-10 mRNA and an apparent decrease in IFN-gamma mRNA in the isl ets of NOD mice which were administered rIL-4. These results suggested that autoreactive CD45RB(low)CD4(+) T helper 2 (Th2)-like cells which developed following rIL-4 administration were predominant in the infi ltrate of the islets, and overt diabetes was prevented. On the other h and, when splenocytes from rIL-4-treated NOD mice were transferred to irradiated NOD recipients, along with splenocytes from diabetic NOD mi ce, all of the recipient mice became diabetic within 8 weeks after tra nsfer. Considered together, a supplement of rIL-4 administered to NOD mice may protect against autoimmune diabetes by facilitating the devel opment of Th2-like autoreactive T cells in the islets. (C) 1998 Academ ic Press.