High-risk corneal allografts and why they lose their immune privilege.
OBJECTIVE
Corneal allografts are routinely performed without HLA typing or systemic immunosuppressive drugs. However, certain conditions create high risks for immune rejection. This review discusses recent insights into the mechanisms that rob the corneal allograft of its immune privilege.


RESULTS
Studies in mice have revealed that stimuli that induce new blood vessel growth in the cornea also elicit proliferation of lymph vessels. Lymph vessels facilitate migration of antigen-presenting cells to regional lymph nodes in which they induce alloimmune responses. The presence of blood vessels in the corneal graft bed creates a unique chemokine milieu that stimulates recruitment of sensitized lymphocytes into the corneal allograft. Other data indicate that although corneal allograft survival is closely associated with Foxp3 expression in CD4+CD25+Foxp3+ T regulatory cells (Tregs), reduced expression of Foxp3 in Tregs creates a high risk for graft rejection. Recent evidence indicates that allergic diseases have a profound impact on the immune response and produce a dramatic increase in corneal allograft rejection.


CONCLUSIONS
Understanding the underlying mechanisms that create 'high-risk' hosts may provide important therapeutic targets for restoring immune privilege of corneal allografts and enhancing their survival.
Niederkorn
Jerry Y
JY
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. jerry.niederkorn@utsouthwestern.edu
D000818:Animals; D016039:Corneal Transplantation; D051858:Forkhead Transcription Factors / Q000276:immunology; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000276:immunology*; D007108:Immune Tolerance; D007249:Inflammation; D051379:Mice; D009389:Neovascularization, Pathologic / Q000276:immunology*; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors