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Dale S. Gregerson, Neal D. Heuss, Ute Lehmann, Scott W. McPherson; Quiescent Retina Promotes The Generation Of Foxp3+ Tregs. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2266.
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The presence, phenotype, and function of T cells in normal retina has received relatively little attention. The paradigm in which access to the retina is limited to activated T cells remains quantitatively accurate, but may not accurately describe the normal retina. We propose a dynamic balance of lymphocytic perusal of the retinal parenchyma that contributes to the day-to-day homeostasis of the retina, based on the following studies.
Retinas were collected from several Tg strains on B6. These include BG1 (CD8) and BG2 (CD4) T cell receptor Tg mice that recognize B-galactosidase (Bgal). These mice were crossed with Foxp3-DTR/GFP mice to permit detection of Foxp3+ regulatory T cells (Tregs). Analysis of T cells in retina was done by flow cytometry and fluorescence microscopy. Rag-deficient mice were used as controls. Injury included an optic nerve crush (ONC) and harvest 3-7 days post-crush. Bgal (1-5 microg) antigen, or saline, was injected into the anterior chamber (AC); retina was harvested 2 days later.
Normal B6 retina contained 68 +/- 45 T cells; similar numbers were found in retina from BG2 and BG1 TCR Tg mice. Retina from B6 eyes injected with saline contained 57 +/- 25 T cells, similar to retinas from BG2 and BG1 mice. Normal B6 retinas contained 52 +/- 30 T cells after injection of Bgal; but BG2 and BG1 retinas showed significant increases in T cells after Bgal injection (149 +/- 84 (p=0.01) and 141 +/- 93 (p=0.05)), respectively. Control retina from Rag KO eyes revealed background staining (approximately 2 cells/retina). An ONC injury also induced an increase in T cells; sham ONC retina contained 59 +/- 37 T cells, and ONC retina contained 120 +/- 91 (p=0.05). Tregs were most strongly affected; BG2 x Foxp3-GFP mice contained 3 +/- 1Foxp3+ T cells/normal retina (6% of total CD3+); saline injection raised that to 8 +/- 7 Foxp3+ T cells/retina (13% of total CD3+); Bgal injection generated 62 +/- 58 Foxp3+ T cells/retina (31% of total CD3+).
Retina contains a small population of T cells with a proportionate number of Tregs. The frequency increased rapidly and substantially upon introduction of specific antigen (Bgal), and included a disproportionately high frequency of Tregs. Minor perturbations (saline or Bgal injection into mice without Bgal-specific T cells) had little effect on retinal T cells. A significant injury (ONC) induced a detectable increase in T cells by day 2 post-injury. We propose that the T cell population of retina is capable of a rapid response that includes a propensity to generate Tregs.
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