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C. N. Stevens, P. W. Chen, J. K. Mellon, E. S. Mayhew, J. Y. Niederkorn; CD4+CD25+ Regulatory T Cells Contribute to the Immune Privilege of Corneal Allografts. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2514.
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Recipients of orthotopic corneal allografts experiencing prolonged graft survival develop regulatory T cells that suppress immune responses to donor alloantigens. CD4+CD25+ regulatory T cells (Treg) play an important role in maintaining immune privilege in the eye, in part, by producing IL-10. Recent studies in liver, skin and cardiac transplantation demonstrate that CD4+CD25+ Treg cells play an important role in the long-term allograft survival. We hypothesize that CD4+CD25+ Treg contribute to the immune privilege exhibited by corneal allografts.
Corneal allografts were performed by surgically removing 2mm cornea buttons from donor mice and were sewn into place on the recipient mice with 11-0 running suture. Depletion of CD4+CD25+ Treg cells was performed by administering anti-CD25 antibody weekly. IL-10 was depleted by administering weekly doses of anti-IL-10 antibody. Balb/c mice were adoptively transferred with either CD4+CD25+ Treg cells or CD4+CD25- T cells isolated by MACS bead separation from naïve Balb/c mice prior to receiving B6 corneal allografts.
Splenectomy of recipient CB6F1 mice exacerbated rejection of NZB donor corneal allografts compared to normal controls. Depletion of CD4+CD25+ Treg cells with anti-CD25 antibody in CB6F1 or Balb/c recipients significantly increased the incidence and tempo of NZB or B6 donor corneal allograft rejection compared to the isotype control group. IL-10 depleted recipient mice exhibited accelerated and universal corneal allograft graft rejection. Adoptive transfer of CD4+CD25+ Treg cells into Balb/c recipient mice decreased the incidence of B6 corneal allograft rejection compared to recipient mice adoptively transferred with CD4+CD25- T cells (20% rejection vs. 50% rejection).
Immune privilege experienced by corneal allografts is due, in part, to the generation of CD4+CD25+ regulatory T cells in the eye and implies that IL-10 production by Treg cells and NKT cells is critical for corneal allograft survival. Augmenting CD4+CD25+ Treg cells in corneal allograft recipients may be a feasible strategy to blunt immune rejection of corneal allografts and improve long-term graft survival.
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