April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Dissociation of Treg Activity for Effector Functions in Mice With and Without Retinal Beta-Galactosidase Expression
Author Affiliations & Notes
  • D. S. Gregerson
    Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • N. D. Heuss
    Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • U. Lehmann
    Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • S. W. McPherson
    Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • Footnotes
    Commercial Relationships  D.S. Gregerson, None; N.D. Heuss, None; U. Lehmann, None; S.W. McPherson, None.
  • Footnotes
    Support  NIH R01EY011542, R01EY16376, and T32EY07133, Research to Prevent Blindness, Inc, and the Minnesota Lions Clubs.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5919. doi:
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    • Get Citation

      D. S. Gregerson, N. D. Heuss, U. Lehmann, S. W. McPherson; Dissociation of Treg Activity for Effector Functions in Mice With and Without Retinal Beta-Galactosidase Expression. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5919.

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

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Abstract

Purpose: : We previously showed that regulatory T cells (Tregs) developed in mice based on the retinal expression of beta-galactosidase (Bgal) in retinal photoreceptor cells. The activity of these Tregs was compared to that of Tregs isolated from wild-type mice, or from T cell receptor transgenic (Tg) mice specific for Bgal (BgalTCR mice).

Methods: : Tg expression of Bgal controlled by the retinal photoreceptor cell arrestin promoter (arrBgal mice) was used as the source of retinal antigen (Ag), and as a source of both Bgal- and retinal Ag-specific Tregs. BgalTCR mice were used as a source of naive or Ag-experienced CD4 T cells, and Bgal-specific Tregs. Tregs were also isolated from normal, non-Tg mice. Isolation of Tregs was based on CD25 expression. The activities of the Tregs were tested by assaying for their effects on EAU induction, DTH, lymphopenia induced proliferation (LIP), and Ag-stimulated cytokine production.

Results: : CD25+ Tregs from wild-type or BgalTCR mice were both capable of inhibiting EAU, consistent with the presence of retinal Ag-specific Tregs, as well as Bgal-specific Tregs, acting locally to limit pathogenesis of EAU. Since several retinal Ags, including IRBP co-localize with the Bgal target of the effector T cells, bystander mechanisms appear to contribute to the inhibition of disease. LIP of BgalTCR T cells was also inhibited by retinal Ag-specific Tregs. Conversely, Bgal-specific Tregs were required to inhibit the ear swelling assay for DTH. Since the ear swelling assay is done by injection of purified Bgal Ag the results indicate that Ag-specific, but not bystander mechanisms were needed to limit DTH. Bgal-specific Tregs were required to inhibit the cytokine production of BgalTCR T cells stimulated in vitro, and support the need for Ag specificity if other specificities are not present.

Conclusions: : These results are consistent with the hypothesis that the contributions of Tregs with multiple Ag specificities provide protection for the retina from inflammation due to autoimmunity to a single retinal self-Ag. This strategy would promote protection for a vital tissue.

Keywords: immunomodulation/immunoregulation • autoimmune disease • immune tolerance/privilege 
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