Two different regulatory T cell populations that promote corneal allograft survival.
OBJECTIVE
To compare and contrast the T regulatory cells (Tregs) induced by anterior chamber (AC) injection of antigen with those induced by orthotopic corneal allografts.


METHODS
Anterior chamber-associated immune deviation (ACAID) Tregs were induced by injecting C57BL/6 spleen cells into the AC of BALB/c mice. Delayed-type hypersensitivity responses to C57BL/6 alloantigens were evaluated by a conventional ear swelling assay. Corneal allograft Tregs were induced by applying orthotopic C57BL/6 corneal allografts onto BALB/c hosts. The effects of anti-CD25, anti-CD8, anti-interferon-γ (IFN-γ), anti-IL-17A, or cyclophosphamide treatments on corneal allograft survival and ACAID were evaluated.


RESULTS
Administration of either anti-CD25 or anti-IFN-γ antibodies prevented the expression of ACAID and abolished the immune privilege of corneal allografts. By contrast, in vivo treatment with anti-CD8 antibody abrogated ACAID but had no effect on corneal allograft survival. Further discordance between ACAID and corneal allograft survival emerged in experiments in which the induction of allergic conjunctivitis or the administration of anti-IL-17A abolished the immune privilege of corneal allografts but had no effect on the induction or expression of ACAID.


CONCLUSIONS
Although orthotopic corneal allografts are strategically located for the induction of ACAID by the sloughing of corneal cells into the AC, the results reported here indicate that the Tregs induced by orthotopic corneal allografts are remarkably different from the Tregs that are induced by AC injection of alloantigen. Although both of these Treg populations promote corneal allograft survival, they display distinctly different phenotypes.
Cunnusamy
Khrishen
K
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA.
Paunicka
Kathryn
K
Reyes
Nancy
N
Yang
Wanhua
W
Chen
Peter W
PW
Niederkorn
Jerry Y
JY
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D000906:Antibodies / Q000008:administration & dosage; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000276:immunology; D016039:Corneal Transplantation; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011058:Pollen; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous
D000906:Antibodies; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens; D007371:Interferon-gamma; D003520:Cyclophosphamide