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N Kitaichi, K Namba, AW Taylor; The Uveitic Ocular Microenvironment Reimposes Tolerance To Autoantigens Through The Induction Of Regulatory T Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1537.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Previously, we found that mice recovering from experimental autoimmune uveoretinitis (EAU) have induced regulatory T cells in their spleens that can suppress uveoretinitis in other EAU-susceptible mice. Also, the induction of these regulatory T cells is not dependent on the mechanisms of ACAID but does depend on the ocular microenvironment. Here, we further characterize the regulatory T cells and mechanisms that can lead to their induction in mice recovering from EAU. Methods: EAU was induced by immunizing with human interphotoreceptor binding protein peptide (IRBPp) with complete Fruend's adjuvant. This was done to B10.RIII, C57BL/6, and melanocortin 5 receptor knockout mice (MC5rKO; mice that lack the key receptor for alpha-melanocyte stimulating hormone (α-MSH) mediated induction of regulatory T cells). An injection of pertussis toxin was required for the C57BL/6 mice. When the uveoretinitis resolved, the spleen T cells were collected and activated in vitro with antigen-pulsed antigen presenting cells. The T cells were adoptively transferred into syngeneic EAU-susceptible mice. Every 3 days we conducted an ocular fundus examination and graded the inflammation on a 5-point scale. Incidence of EAU was considered positive when a mouse had at least a score of 2 in one of the eyes. Results: CD4 T cells from spleens of mice recovering from EAU were isolated, and antigen activated. When we adoptively transferred these cells into other EAU-susceptible mice both, the incidence and severity of uveoretinitis were suppressed. This was in contrast to the severe and 100% incidence of EAU we observed in EAU-susceptible B10.RIII mice that received an injection of activated CD4 T cells from spleens of naive mice. In addition, we observed no significant change in the severity and incidence of EAU between the MC5rKO mice and their normal control C57BL/6 mice. Conclusion: There is in mice with EAU the induction of CD4 regulatory T cells. The induction is neither dependent on the mechanisms of ACAID nor on α-MSH. But, it is still dependent on the ocular microenvironment. This suggests that even during an episode of autoimmune uveitis the ocular microenvironment uses some mechanism of immunosuppression to induce the activation of regulatory T cells that may suppress and prevent further episodes of autoimmune uveitis.
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