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R.E. Cone, X. Li, R. Sharafieh, J. O'Rourke, A.T. Vella; Intracameral Antigen Induces QA–1– Restricted Splenic Regulatory (Supressor) T Cells That Require Interferon–Gamma to Induce Immunosuppression . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5152.
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© ARVO (1962-2015); The Authors (2016-present)
The generation of peripheral regulatory T cells is an effective mechanism to protect sites such as the eye that are particularly vulnerable to immune and/or inflammatory attack. Splenic T cells that regulate cell–mediated immunity are induced by intracameral antigen injection (AC–SPL cells). Here we investigated the influence of interferon–Î³ and the restriction by Qa–1 antigens on the activity and antigen specificity of AC–SPL CD8+ suppressor T cells that suppress directly delayed–type hypersensitivity (DTH).
CD8+ AC–SPL cells were recovered from both naïve mice and mice immunized with TNP–BSA antigen. Both groups received an intracameral injection of TNP–BSA. AC–SPL suppressor T cells were quantified by the adoptive transfer of AC–SPL cells into the footpads of mice immunized to TNP–BSA after challenge with epicutaneous picryl chloride (PCl) ie to elicit Delayed Type Hypersensitivity (DTH) to TNP. The influence of IFN–Î³ on the activation and/or maintenance of AC–SPL suppressor T cells was investigated by the generation of these cells in IFN–Î³ +/+, and –/– mice. Next, Qa–1 restriction of the suppressive activity of the AC–SPL cells was investigated by the determination of suppressive activity of AC–SPL cells in mice that differ in MHC class I or Qa–1.
I) The footpad injection of CD8+ AC–SPL cells into TNP–BSA–primed mice suppressed DTH after challenge with PCl. II) Immunization with TNP–BSA prior to the intracameral injection of TNP–BSA increased by at least 5–fold the number of AC–SPL suppressor T cells induced by the intracameral injection of TNP–BSA compared to naïve mice. III) The suppression of DTH by the AC–SPL cells was Qa–1– restricted but not MHC I–dependent. IV) AC–SPL suppressor T cells recovered from IFN–Î³–/– mice did not suppress DTH unless IFN–Î³ was included with the inoculum of AC–SPL cells into the footpads of recipient mice that were challenged. V) AC–SPL suppressor T cells express receptors for IFN–Î³. The AC–SPL suppressor T cells are produced in perforin –/– mice indicating that they are not canonical cytotoxic T cells.
An immunization that induces cell–mediated immunity amplifies the number of splenic suppressor T cells induced by intracameral antigen. IFN–Î³ is required for this immunosuppressive activity, but the generation of AC–SPL suppressor T cells does not require IFN–Î³.
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