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CD8⁺ T Regulatory Cells Use a Novel Genetic Program that Includes CD103 to Suppress Th1 Immunity in Eye-Derived Tolerance

¹From the Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

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-ß2-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-ß 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-ß2-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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