May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
CD4+CD25+ Regulatory T Cells Contribute to the Immune Privilege of Corneal Allografts
Author Affiliations & Notes
  • C. N. Stevens
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • P. W. Chen
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • J. K. Mellon
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • E. S. Mayhew
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • J. Y. Niederkorn
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • Footnotes
    Commercial Relationships  C.N. Stevens, None; P.W. Chen, None; J.K. Mellon, None; E.S. Mayhew, None; J.Y. Niederkorn, None.
  • Footnotes
    Support  NIH EY07641 and an unrestricted grant from Research to Prevent Blindness, Inc.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2514. doi:https://doi.org/
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    • Get Citation

      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. doi: https://doi.org/.

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

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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).

Conclusions: : 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.

Keywords: immune tolerance/privilege • cornea: basic science • immunomodulation/immunoregulation 
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