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S. K. Chauhan, D. R. Saban, R. Dana; Increased Frequency of CD4+CD25+FoxP3+ Regulatory T Cells in the Murine Model of Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):193. doi: https://doi.org/.
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To investigate the frequency and distribution of CD4+CD25+FoxP3+ regulatory T cells (Tregs) in corneal allograft recipients. Tregs have been shown to play a central role in inducing and maintaining transplant tolerance in various experimental models including skin, cardiac and islet transplantation.
Fully disparate corneal grafts from C57Bl/6 (H-2b) mice were orthotopically transplanted in normal-risk BALB/c (H-2d) recipient mice. Three-color flow cytometry for Treg markers (CD4+ CD25+ FoxP3+) was employed for enumeration of Tregs in the spleen and regional draining lymph nodes of naïve and allograft recipient mice at various time points post-transplantation. Treg frequencies were calculated as percentages of CD4+ T cells.
Corneal allograft recipient mice, compared to naïve mice, showed significantly higher frequencies of Tregs in the spleen (mean±SD: 9.05 ± 1.86% versus 5.46 ± 0.32 %; p=0.011) as well as the draining lymph nodes (9.342 ± 1.17% versus 6.19 ± 0.33%; p=0.04). In addition, a significant trend of continuous increase in Treg frequencies from the day of transplantation to induction phase (1-2 week post-transplantation) and maintenance phase (>5 weeks post-transplantation) was observed in both the spleen and draining lymph nodes of transplanted recipients.
Our data demonstrate higher frequencies of Tregs in the lymphoid tissues of allograft recipients, suggesting the possible involvement of these cells in the regulation of alloimmunity. This may account for the relatively high survival rates of corneal allografts, even without systemic immune suppression, as compared to other solid tissue/organ transplants.
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