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Antonio Di Zazzo, Brinda Subbarayal, Thomas H Dohlman, Takenori Inomata, Sunil Chauhan, Reza Dana; The contribution of T cells to corneal angiogenic privilege in transplantation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4875.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of T effector cells (Teffs) and/or regulatory T cells (Tregs) from high-risk (HR) or low-risk (LR) transplanted mice on vascular endothelial cell (VEC) proliferation.
Ipsilateral lymph nodes were collected from Balb/c mice 14 days after low-risk and high-risk corneal transplantation. CD4+CD25- effector T cells and CD4+CD25+ Tregs, sorted by magnetic beads and stimulated with anti-CD3, were co-cultured in a 96-well plate with MILE SVEN 1 cells, a vascular endothelial cell line, in DMEM/FBS10%. VEC proliferation was measured using the BrdU incorporation assay 19 hours after coculturing.
CD4+CD25- Teffs from HR and LR transplanted mice significantly promoted VEC proliferation compared with positive (VEGF-A 20ng/ml) and negative controls. VEC proliferation was significantly higher when cocultured with Teffs from HR than Teffs from LR and naïve mice (Teff HR 0.9 ± 0.03;Teff LR 0.7234 ± 0.1; VEGF-A 0.6 ± 0.03; Negative Control: 0.5± 0.02 p<0.0001). After culturing Teffs and VECs with CD4+CD25+ Tregs from transplanted mice, VEC proliferation was significantly decreased compared with VECs cultured with Teffs alone (Teff 0.9 ± 0.03; Teff+Treg 0.6 ± 0.06; p<0.0005). Tregs alone had no effect on VEC proliferation.
Our data show that CD4+CD25- effector T cells isolated from HR and LR transplanted mice directly induce VEC proliferation. Further, Tregs inhibitTeff cell-mediated VEC proliferation. Our results suggest that a balance between pro-aniogenic Teffs and anti-angiogeneic Tregs is essential to sustain angiogenic privilege in HR corneal
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