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 Apr;47(4):1533-42. doi: 10.1167/iovs.04-1454.

Abstract

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-beta2-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-beta 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-beta2-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • CD8-Positive T-Lymphocytes / physiology*
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Profiling
  • Hypersensitivity, Delayed / immunology
  • Immune Tolerance / genetics*
  • Immunity
  • Integrin alpha Chains / genetics*
  • Integrin alpha Chains / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Ovalbumin / immunology
  • Receptors, Antigen, T-Cell / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / physiology*
  • Th1 Cells / immunology*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta2
  • Up-Regulation

Substances

  • Antigens, CD
  • Integrin alpha Chains
  • Receptors, Antigen, T-Cell
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2
  • alpha E integrins
  • Ovalbumin