Abstract
Abstract: :
Purpose: Oral tolerance as a treatment for uveitis is efficient in the rat model of EAU and was already applied clinically. For oral tolerance in other disease models, such as experimental autoimmune encephalomyelitis, bystander suppression in the target organ of autoimmunity was postulated as an important mechanism, permitting induction of tolerance with any antigen present in the affected organ. However, this mechanism is questioned to be active in uveitis, therefore we here investigated local effects of bystander suppression in rat EAU. Methods: Naive Lewis rats were fed with Ovalbumin (OVA) 3 times to induce oral tolerance. During oral tolerization rats were immunized with S–Ag peptide PDSAg for induction of EAU. OVA or PBS as a control were injected into the eyes of immunized as well as non–immunized animals 5 or 8 days post immunization. Rats were followed clinically until uveitis subsided in control groups. Histology was performed from all eyes. Results: Oral tolerance to OVA and subsequent intraocular injection of OVA did not reduce PDSAg–induced uveitis, independently of the time point the tolerizing antigen was injected intraocularly. In untolerized animals the severity of PDSAg–induced uveitis was not intensified by ocular injection (PBS or OVA). Oral OVA could not induce uveitis in non–immunized animals that received intraocular OVA. Conclusions: Intraocular presentation of the tolerogen is obviously not sufficient to attract orally induced regulatory T cells to the eye. This leads to the conclusion that orally induced bystander suppression is not mediated in the eye, if an oral tolerogen is injected into the target organ.
Keywords: autoimmune disease • immunomodulation/immunoregulation • uveitis–clinical/animal model