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R. K. Pais, R. E. Cone; Influence of TGF-Beta in the Anterior Chamber on the Generation of the Suppression of Delayed Type Hypersensitivity by the Intracameral Injection of Antigen. Invest. Ophthalmol. Vis. Sci. 2009;50(13):831.
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The injection of antigen into the anterior chamber (AC) induces the suppression of specific cell-mediated immunity by anterior chamber associated immune deviation(ACAID). F4/80+ monocytes take up the antigen in the anterior chamber and are present in the circulation 24 hr after intracameral injection. These cells migrate to the spleen and thymus and participate in the generation of antigen-specific regulatory T cells. While the cytokines TGF-b, alpha-MSH and VIP in aqueous humor are known to be responsible for the induction of a suppressive phenotype for F4/80+ cells in vitro, the individual contribution of these cytokines in vivo requires clarification. Therefore we investigated the requirement for TGF-b in the anterior chamber for the generation of ACAID.
Anti-TGF-b1-3 blocking antibody or control antibody along with Ovalbumin (OVA) was injected into the AC of Balb/c mice. One week after these mice were immunized with OVA, delayed type of hypersensitivity (DTH) was measured by the intradermal injection of OVA into a footpad and measurement of swelling of the footpad 24 hr later. A similar protocol of immunization and DTH measurement was also done in mice that received i.v peripheral blood mononuclear cells (PBMC) from mice that received an intracameral injection of OVA (AC-PBMC) and/or anti-TGF-b. The requirement of the PI3Kinase/Akt pathway as a mediator in ACAID was studied by intracameral injection of the PI3Kinase inhibitors wortmannin and LY294002 with OVA.
Intracameral injection of blocking antibody to TGF-b with OVA significantly reduced the suppression of DTH in mice. Moreover AC-PBMCs from these mice did not transfer the suppression of DTH. This blocking effect of anti-TGF-b could be rescued by adoptively transferring PBMCs from mice that received an intracameral injection of OVA. Similar to the intracameral injection of anti-TGF-b, the blockade of the PI3Kinase /Akt pathway in the anterior chamber reduced the suppression of DTH.
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