Behavioural conditioning of immune response with cyclosporine A in a model of experimental autoimmune uveitis (EAU) mitigates Th1 immune response but antagonizes Th17 responses

Abstract

Purpose: To examine the influence of behavioural conditioning with cyclosporine A (CsA) on the outcome of Th1/Th17 driven experimental autoimmune uveoretinitis (EAU) in B10.RIII mice.

Methods: Animals were placed on a water deprivation regimen. On day 10, the conditioning procedure started: Mice received a 0.2% w/v saccharin solution as conditioned stimulus combined with CsA (20 mg/kg) in six association trials with 72h intervals. For evocation, conditioned mice were re-exposed to saccharin, whereas the sham-conditioned group received water only. The evocation trials were pursued until the end of the experiment. After the third evocation trial (day 31), all animals were immunized with hIRBPp161-180 peptide in CFA and a concomitant injection of pertussis toxin. One hour after the last evocation (day 51, +1h) the animals were sacrificed; eyes were collected for histology; splenocytes were cultured, and analyzed by ELISA for various cytokines.

Results: Behavioural conditioned and evocated mice had no improvement of EAU with respect to incidence and severity of disease. ELISA analysis revealed that the Th1 response of mice was reduced with a shift towards Th2 and Th17 cytokine profiles. Adoptive transfer of antigen-specific splenocytes from conditioned and evocated mice to healthy mice resulted in a decreased severity of EAU as compared to the control group.

Conclusions: We conclude that conditioning of immune responses with CsA mitigates Th1 but maintains Th17 autoimmune responses and does not improve Th1/Th17 mediated EAU. Thus, behavioural conditioning may regulate the immune mechanism of autoimmune diseases.

Keywords: 746 uveitis-clinical/animal model • 432 autoimmune disease • 489 cyclosporine