title: Severing corneal nerves in one eye induces sympathetic loss of immune privilege and promotes rejection of future corneal allografts placed in either eye.
abstract: Less than 10% of corneal allografts undergo rejection even though HLA matching is not performed. However, second corneal transplants experience a threefold increase in rejection, which is not due to prior sensitization to histocompatibility antigens shared by the first and second transplants since corneal grafts are selected at random without histocompatibility matching. Using a mouse model of penetrating keratoplasty, we found that 50% of the initial corneal transplants survived, yet 100% of the subsequent corneal allografts (unrelated to the first graft) placed in the opposite eye underwent rejection. The severing of corneal nerves that occurs during surgery induced substance P (SP) secretion in both eyes, which disabled T regulatory cells that are required for allograft survival. Administration of an SP antagonist restored immune privilege and promoted graft survival. Thus, corneal surgery produces a sympathetic response that permanently abolishes immune privilege of subsequent corneal allografts, even those placed in the opposite eye and expressing a completely different array of foreign histocompatibility antigens from the first corneal graft.
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: K J
authors: KJ
authors: Paunicka
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: J
authors: J
authors: Mellon
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: D
authors: D
authors: Robertson
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: M
authors: M
authors: Petroll
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: J R
authors: JR
authors: Brown
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: J Y
authors: JY
authors: Niederkorn
mesh_terms: D064591:Allografts; D000818:Animals; D003315:Cornea / Q000294:innervation*; D016039:Corneal Transplantation; D003714:Denervation / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000503:physiopathology; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D006649:Histocompatibility Antigens / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011984:Sensory Receptor Cells; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
chemical_list: D006649:Histocompatibility Antigens; D013373:Substance P
keywords: Basic (laboratory) research/science; corneal transplantation/ophthalmology; immune regulation; rejection; tolerance: experimental