Depletion of Thymus-Derived CD4⁺CD25⁺ T Cells Abrogates the Suppressive Effects of α-galactosylceramide Treatment on Experimental Allergic Conjunctivitis

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Background: We showed previously that α-galactosylceramide (α-GalCer) treatment elevated splenic CD4⁺CD25⁺Foxp3⁺ T-cell numbers and suppressed the development of experimental allergic conjunctivitis (EC). Here, we investigated whether CD4⁺CD25⁺Foxp3⁺ T cells mediate the suppressive effects of α-GalCer treatment on EC.
Methods: To deplete CD4⁺CD25⁺Foxp3⁺ T cells, neonatal mice were thymectomized and intraperitoneally injected with anti-CD25 Ab. At 6 weeks of age, these mice were immunized with ragweed (RW) in aluminum hydroxide. Ten days later, the mice were challenged with RW in eye drops and 24 hours later, the conjunctivas and spleens were harvested for histological and flow cytometric analyses, respectively. α-GalCer or vehicle was injected 2 hours prior to RW challenge. In addition, α-GalCer was injected into thymus-intact EC-developing mice that had not been treated with anti-CD25 Ab.
Results: α-GalCer treatment significantly suppressed EC in the thymus-intact mice that had not been treated with anti-CD25 Ab. In contrast, α-GalCer treatment of thymectomized and anti-CD25 Ab-treated mice did not affect the severity of EC or splenic CD4⁺CD25⁺Foxp3⁺ T-cell numbers. However, α-GalCer treatment did significantly increase splenic CD4⁺CD25⁺Foxp3⁺ T-cell numbers in thymectomized mice that had not received anti-CD25 Ab.
Conclusions: α-GalCer treatment during the effector phase of EC increased CD4⁺CD25⁺Foxp3⁺ T-cell numbers, which in turn suppressed the development of EC.