INTERLEUKIN-2 TREATMENT POTENTIATES INDUCTION OF ORAL TOLERANCE IN A MURINE MODEL OF AUTOIMMUNITY

The present study addresses the feasibility of potentiating oral toler ance by immunomanipulation, using the murine model of experimental aut oimmune uveoretinitis (EAU) induced by immunization with the retinal a ntigen interphotoreceptor retinoid binding protein (IRBP). Three feedi ngs of 0.2 mg IRBP every other day before immunization did not protect against EAU, whereas a similar regimen of five doses was protective. However, supplementing the nonprotective 3X regimen with as little as one injection of 1,000 U of human recombinant interleukin-2 (IL-2) res ulted in disease suppression that was equal to that of the protective 5X regimen. The protective effect was maintained across a range of IL- 2 doses and times of administration; none of the IL-2 regimens tested resulted in disease enhancement. Peyer's Patch cells of 3X-fed and IL- 2-treated mice showed greatly increased production of TGF-beta, IL-4, and IL-10 compared with animals given the nonprotective 3X regimen and to animals given the protective 5X regimen. We propose that IL-2 trea tment enhances protection from EAU at least in part by stimulating pro duction of antiinflammatory cytokines by regulatory cells in Payer's P atches. Moreover, the observed lymphokine production patterns suggest that whereas protection induced by the 3X + IL-2 regimen is likely to involve antiinflammatory cytokines, protection induced by the 5X regim en might involve anergy or deletion of the uveitogenic T cells. These results could have practical implications for use of IL-2 as a safe an d effective way of potentiating oral tolerance.