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Dirk Bauer, Martin Busch, Lena Bagnewski, Maren Hennig, Hanna Bähler, Manfred Schedlowski, Solon Thanos, Arnd Heiligenhaus; Behavioural conditioning of immune response with cyclosporine A in a model of experimental autoimmune uveitis (EAU) mitigates Th1 immune response but antagonizes Th17 responses. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5307.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
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