Regulation of CD8+ T cell responses to retinal antigen by local FoxP3+ regulatory T cells

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Abstract

While pathogenic CD4T cells are well known mediators of autoimmune uveoretinitis, CD8 T cells can also be uveitogenic. Since preliminary studies indicated that C57BL/6 mice were minimally susceptible to autoimmune uveoretinitis induction by CD8 T cells, the basis of the retinal disease resistance was sought. Mice that express ß-galactosidase (ßgal) on a retina-specific promoter (arrßgal mice) were backcrossed to mice expressing green fluorescent protein (GFP) and diphtheria toxin (DTx) receptor (DTR) under control of the Foxp3 promoter (Foxp3-DTR/GFP mice), and toT cell receptor transgenic mice that produce ßgalspecific CD8 T cells (BG1 mice). These mice were used to explore the role of regulatory T cells in the resistance to retinal autoimmune disease. Experiments with T cells from double transgenic BG1 × Foxp3-DTR/GFP mice transferred into Foxp3-DTR/GFP × arrßgal mice confirmed that the retina was well protected from attempts to induce disease by adoptive transfer of activated BG1 T cells. The successful induction of retinal disease following unilateral intraocular administration of DTx to deplete regulatory T cells showed that the protective activity was dependent on local, toxin-sensitive regulatoryT cells; the opposite, untreated eye remained disease-free. Although there were very few Foxp3+ regulatory T cells in the parenchyma of quiescent retina, and they did not accumulate in retina, their depletion by local toxin administration led to disease susceptibility. We propose that these regulatory T cells modulate the pathogenic activity of ßgal-specific CD8 T cells in the retinas of arrßgal mice on a local basis, allowing immuno regulation to be responsive to local conditions.

Original languageEnglish (US)
Article numberArticle 166
JournalFrontiers in immunology
Volume3
Issue numberJUN
DOIs
StatePublished - 2012

Keywords

  • Autoimmunity
  • EAU
  • Foxp3
  • Retina
  • Tregs

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