May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
B7+ Iris Pigment Epithelial Cells Convert Naïve T Cells into CTLA–4+, B7–Expressing CD8+ Regulators
Author Affiliations & Notes
  • S. Sugita
    Dept of Ophthalology, Schepens Eye Research Institute, Boston, MA
  • J.W. Streilein
    Dept of Ophthalology, Schepens Eye Research Institute, Boston, MA
  • Footnotes
    Commercial Relationships  S. Sugita, None; J.W. Streilein, None.
  • Footnotes
    Support  NIH Grant EY 05678
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1009. doi:
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      S. Sugita, J.W. Streilein; B7+ Iris Pigment Epithelial Cells Convert Naïve T Cells into CTLA–4+, B7–Expressing CD8+ Regulators . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1009.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Ocular pigment epithelia (PE) contribute to ocular immune privilege by converting T cells they encounter into regulators. The goal of this study was to determine whether B7 family molecules expressed by PE are necessary for this conversion. Methods: Adult C57BL/6 mice served as donors of ocular PE and splenic T cells. Mice with disrupted genes for CTLA–4, CD28, CD80 and/or CD86 were used. Naïve T cells (PE Tregs), first exposed to cultured PE cells, were harvested, x–irradiated, then added fresh T cells (responder T cells) plus anti–CD3 abs. Anti–CD80/CD86 abs, recombinant CTLA–4 fusion protein, or anti–CTLA–4 abs were included in the cultures in which naïve T cells and IPE cells were present. Proliferation was assessed for uptake of [3H]–thymidine. IPE Tregs were examined by RT–PCR for expression of B7–1 & B7–2. Results: While naïve T cells, with or without Tcr ligation, acquire the capacity to suppress by sander T cell activation when exposed to iris PE (IPE), ciliary body PE) and retina PE, only IPE required direct contact with T cells to achieve this effect. B7–1 and B7–2 proved to be the relevant surface molecules on IPE. Moreover, only T cells capable of expressing CTLA–4, as well as B7–1 & B7–2, were able to acquire the regulatory phenotype, Tregs generated upon exposed to IPE were almost exclusively CD8+ and secreted active TGFb. Conclusions: Inhibition of T cell pathogenesis in the ocular anterior segment is achieved because IPE hijack immune co–stimulation molecules to generate TGFb–producing T cells that in turn use similar co–stimulation to contact and suppress bystander T cells.

Keywords: immune tolerance/privilege • iris • cell–cell communication 
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