BACKGROUND: We showed previously that treatment with an agonistic anti-4-1BB Ab during the induction phase of murine experimental allergic conjunctivitis (EC) suppresses the development of this model disease. It was reported that 4-1BB promotes the expansion of regulatory T cells. Here we asked whether the suppression of EC by agonistic anti-4-1BB Ab treatment is mediated by regulatory T cells. METHODS: Neonatal BALB/c mice were thymectomized and intraperitoneally injected with anti-CD25 Ab. At 6 weeks of age, these mice were immunized with ragweed (RW) in alum. As a control, immunocompetent BALB/c mice were immunized. Ten days later, the mice were challenged with RW in eye drops and 24 h later, the conjunctivas and spleens were harvested for histological and flow-cytometric analyses, respectively. The agonistic anti-4-1BB Ab or control normal rat IgG was injected intraperitoneally during the induction phase of EC. RESULTS: With regard to immunocompetent mice, anti-4-1BB Ab treatment significantly suppressed the severity of EC as evaluated by conjunctival eosinophil numbers. In contrast, in thymectomized and anti-CD25 Ab-treated mice in which CD4+CD25+ regulatory T cells were efficiently depleted, anti-4-1BB Ab treatment did not affect the severity of EC. CONCLUSIONS: These results indicate that CD4+CD25+ regulatory T cells play a critical role in the suppression of EC by anti-4-1BB Ab treatment. Copyright 2008 S. Karger AG, Basel.
BACKGROUND: We showed previously that treatment with an agonistic anti-4-1BB Ab during the induction phase of murine experimental allergic conjunctivitis (EC) suppresses the development of this model disease. It was reported that 4-1BB promotes the expansion of regulatory T cells. Here we asked whether the suppression of EC by agonistic anti-4-1BB Ab treatment is mediated by regulatory T cells. METHODS: Neonatal BALB/c mice were thymectomized and intraperitoneally injected with anti-CD25 Ab. At 6 weeks of age, these mice were immunized with ragweed (RW) in alum. As a control, immunocompetent BALB/c mice were immunized. Ten days later, the mice were challenged with RW in eye drops and 24 h later, the conjunctivas and spleens were harvested for histological and flow-cytometric analyses, respectively. The agonistic anti-4-1BB Ab or control normal rat IgG was injected intraperitoneally during the induction phase of EC. RESULTS: With regard to immunocompetent mice, anti-4-1BB Ab treatment significantly suppressed the severity of EC as evaluated by conjunctival eosinophil numbers. In contrast, in thymectomized and anti-CD25 Ab-treated mice in which CD4+CD25+ regulatory T cells were efficiently depleted, anti-4-1BB Ab treatment did not affect the severity of EC. CONCLUSIONS: These results indicate that CD4+CD25+ regulatory T cells play a critical role in the suppression of EC by anti-4-1BB Ab treatment. Copyright 2008 S. Karger AG, Basel.
Authors: Vaiva Vezys; Pablo Penaloza-MacMaster; Daniel L Barber; Sang-Jun Ha; Bogumila Konieczny; Gordon J Freeman; Robert S Mittler; Rafi Ahmed Journal: J Immunol Date: 2011-07-08 Impact factor: 5.422