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Hiroshi Keino, Sharmila Masli, Shuji Sasaki, J. Wayne Streilein, Joan Stein-Streilein; CD8+ T Regulatory Cells Use a Novel Genetic Program that Includes CD103 to Suppress Th1 Immunity in Eye-Derived Tolerance. Invest. Ophthalmol. Vis. Sci. 2006;47(4):1533-1542. doi: 10.1167/iovs.04-1454.
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purpose. The peripheral tolerance that arises after injection of antigen into the anterior chamber (anterior chamber-associated immune deviation; ACAID) is associated in part with CD8+ T cells that suppress the expression of Th1 and Th2 immunity. The purpose of these studies was to determine the genes and molecules that are critical for CD8+ T regulatory cell (T reg) functions in ACAID.
methods. Ovalbumin (OVA)-specific CD8+ T cells from T-cell receptor (TCR) transgenic OT-1 mice acquire efferent regulatory properties similar to in vivo-generated CD8+ T regs after stimulation with OVA-pulsed TGF-β2-treated APCs. Changes in the genetic program associated with acquisition of efferent regulatory function in OT-1 CD8+ T cells in vitro were determined by DNA microarray analyses and confirmed by RT-PCR analyses and biological assays.
results. T regulatory OT-1 T cells acquired a novel transcriptional pattern indicative of their function. Genes for molecules associated with TGF-β function, resistance to TCR-triggered apoptosis, and localization of cells to antigen deposition in peripheral tissues were upregulated, and genes related to cytolytic function were downregulated. Further study showed that CD103, a cell-adhesion molecule that binds E-cadherin, was highly upregulated in in vivo-generated ACAID T regs and was necessary for their suppression of T-cell activation in vitro.
conclusions. OT-1 CD8 T cells modulated in vitro by exposure to antigen-pulsed, TGF-β2-treated APCs expressed genes related to immune suppression. Thus, the necessity for CD103 emerges in the efferent CD8+ T-cell regulatory mechanisms in eye-derived tolerance.
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