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R. E. Cone, S. Chattopadhyay, R. Sharafieh, Y. Lemire, J. O'Rourke, R. A. Flavell, R. B. Clark; Sensitivity to TGF-Beta by T Cells Is Not Required for the Activation of Splenic CD8+ Regulatory T Cells by the Intracameral Injection of Antigen but Is Required for the Suppression of a Delayed Hypersensitivity Reaction by Anterior Chamber-Induced Splenic CD8+ T Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3034.
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The intracameral injection of antigen induces the production of splenic CD8+ regulatory T cells (AC-SPL cells) that suppress effector T cells that induce a delayed type hypersensitivity (DTH) reaction. Because CD8+ regulatory T cells are also induced in vitro by TGF-β or F4/80+ cells exposed to TGF-β and antigen in vitro, we investigated (i) whether sensitivity to TGF-β is required to produce CD8+ AC-SPL cellsafter the intracameral injection of antigen and (ii) for the suppression of a DTH reaction by CD8+ AC-SPL cells.
dnTGFβRII or Cbl-b -/- mice whose T cells are resistant to TGF-β received an intracameral injection of TNP-BSA and then were immunized with TNP-BSA. The ability of total AC-SPL cells and CD8+ AC-SPL cells recovered from these mice to suppress DTH was measured by the injection of these cells into the footpads of TNP-BSA-immunized wildtype recipients after the footpads were challenged with picryl chloride (PCl). TNP-BSA-immunized dnTGFβRII, Cbl-b -/- or wildtype mice were the recipients of wildtype CD8+ AC-SPL cells when challenged with PCl. Immunized wildtype mice received wildtype AC-SPL cells and antibodies to TGF-β when the footpads were challenged with PCl.
DnTGFβRII-immunized and Cbl-b-/- mice produced splenic CD8+ regulatory cells after the intracameral injection of antigen and immunization. The suppression of a DTH reaction by CD8+ AC-SPL cells in wildtype mice was blocked by the local inclusion of antibodies to TGF-β 1-3. Moreover, the DTH reaction in immunized dnTGFβRII and Cbl-b -/- mice was not suppressed by wildtype CD8+ AC-SPL cells.
these observations suggest that T cell sensitivity to TGF-β is not an obligate requirement for the in vivo induction of CD8+ AC-SPL T cells but the suppression of a DTH reaction by CD8+ AC-SPL cells is dependent on TGF-β.
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