title: Surgical denervation of ocular sympathetic afferents decreases local transforming growth factor-beta and abolishes immune privilege.
abstract: Mounting evidence points to a role for the sympathetic nervous system in suppressing inflammation. This role might be of specific relevance for immune privilege in the eye, where, sporadically, patients with denervated sympathetic fibers develop chronic inflammation. The present study used mice to investigate whether the robust innervation of intraocular structures by the sympathetic system plays a role in maintaining ocular immune privilege. We first performed surgical removal of the superior cervical ganglion, which supplies sympathetic fibers to the eye, and studied the immune response generated against soluble antigens or allogeneic tumor cells injected into the ocular anterior chamber under these conditions. Our results show that in the absence of functional sympathetic fibers, the eye loses its ability to prevent either the immune rejection of intraocular allogeneic tumor cells or the suppression of delayed type hypersensitivity responses against soluble antigens injected in the anterior chamber. This loss of immune privilege is accompanied by a decrease in the concentration of transforming growth factor-beta in the aqueous humor. These results suggest that immune privilege is lost in the absence of a functional sympathetic innervation of the eye, allowing intraocular immune responses to become exaggerated. We conclude that ocular sympathetic nerves are critical for the generation and maintenance of immune privilege in the eye through the facilitation of local transforming growth factor-beta production.
authors.affiliation: Schepens Eye Research Institute, 20 Staniford St., Boston, MA 02114, USA.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Vega
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Keino
authors.forename: Sharmila
authors.initials: S
authors.lastname: Masli
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001082:Aqueous Humor / Q000276:immunology; D005123:Eye / Q000276:immunology / Q000294:innervation*; D015171:Ganglionectomy; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007109:Immunity / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology; D015213:Neuroimmunomodulation; D017783:Superior Cervical Ganglion / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D000941:Antigens; D016212:Transforming Growth Factor beta
references.citation: Neuroscience. 2001;107(4):593-602
references.pmid: 11720783
references.citation: J Leukoc Biol. 2006 Jun;79(6):1093-104
references.pmid: 16531560
references.citation: J Immunol. 2002 Nov 1;169(9):5028-35
references.pmid: 12391218
references.citation: J Neuroimmunol. 1995 Aug;61(1):61-70
references.pmid: 7560013
references.citation: J Neurol Sci. 2007 Jan 15;252(1):29-35
references.pmid: 17129587
references.citation: Br J Ophthalmol. 1994 Dec;78(12):949
references.pmid: 7819183
references.citation: Invest Ophthalmol Vis Sci. 1994 Sep;35(10):3702-10
references.pmid: 7522227
references.citation: Exp Neurol. 2007 Sep;207(1):75-84
references.pmid: 17597612
references.citation: J Neuropathol Exp Neurol. 2003 Aug;62(8):848-54
references.pmid: 14503640
references.citation: J Neurosurg. 1991 Nov;75(5):766-73
references.pmid: 1833515
references.citation: Am J Physiol. 1995 Apr;268(4 Pt 1):C910-7
references.pmid: 7733239
references.citation: J Allergy Clin Immunol. 2000 Jan;105(1 Pt 1):91-8
references.pmid: 10629458
references.citation: J Neuroimmunol. 2004 Aug;153(1-2):40-9
references.pmid: 15265662
references.citation: Neuroscience. 2009 Feb 6;158(3):1184-93
references.pmid: 18722511
references.citation: Ann Neurol. 1980 Nov;8(5):520-5
references.pmid: 6254440
references.citation: J Immunol. 1999 Sep 1;163(5):2492-9
references.pmid: 10452985
references.citation: Eur J Immunol. 1992 Jan;22(1):165-73
references.pmid: 1530916
references.citation: J Fr Ophtalmol. 1990;13(11-12):557-61
references.pmid: 2081848
references.citation: Brain Behav Immun. 2000 Dec;14(4):239-55
references.pmid: 11120594
references.citation: Br J Pharmacol. 2001 Nov;134(5):977-84
references.pmid: 11682445
references.citation: J Immunol. 2001 Jan 1;166(1):232-40
references.pmid: 11123297
references.citation: Am J Ophthalmol. 1965 May;59:927-8
references.pmid: 14288941
references.citation: Gut. 2004 Mar;53(3):438-45
references.pmid: 14960531
references.citation: J Neurosurg. 1992 Nov;77(5):694-9
references.pmid: 1403109
references.citation: Invest Ophthalmol Vis Sci. 1996 Feb;37(2):413-24
references.pmid: 8603847
references.citation: Am J Ophthalmol. 2000 May;129(5):672-3
references.pmid: 10844066
references.citation: J Immunol. 2004 Feb 1;172(3):1567-74
references.pmid: 14734736
references.citation: Br J Ophthalmol. 2006 Jul;90(7):812-3
references.pmid: 16782945
references.citation: Clin Exp Allergy. 2008 Jul;38(7):1160-7
references.pmid: 18691294
references.citation: Invest Ophthalmol Vis Sci. 2000 Mar;41(3):811-21
references.pmid: 10711698
references.citation: J Exp Med. 1980 Oct 1;152(4):1121-5
references.pmid: 6775039
references.citation: Histol Histopathol. 2001 Oct;16(4):1135-41
references.pmid: 11642733
references.citation: Trends Pharmacol Sci. 2004 Dec;25(12):640-6
references.pmid: 15530642
references.citation: Hypertension. 2004 Oct;44(4):392-3
references.pmid: 15326090
references.citation: J Leukoc Biol. 2003 Aug;74(2):179-85
references.pmid: 12885934
references.citation: Mol Vis. 2008 Mar 26;14:615-24
references.pmid: 18385797
references.citation: Exp Eye Res. 1976 Mar;22(3):259-65
references.pmid: 1269546
references.citation: Acta Physiol Pharmacol Latinoam. 1987;37(3):305-19
references.pmid: 3332531
references.citation: Arch Ophtalmol Rev Gen Ophtalmol. 1953;13(5):512-3
references.pmid: 13125747
references.citation: Hypertension. 2004 Oct;44(4):410-8
references.pmid: 15326086
references.citation: Pharmacol Rev. 1974 Sep;26(3):199-288
references.pmid: 4376244
references.citation: Invest Ophthalmol Vis Sci. 1989 Feb;30(2):323-9
references.pmid: 2492486
references.citation: Anesth Analg. 2004 Nov;99(5):1508-1515
references.pmid: 15502056
references.citation: Nat Med. 1998 Jul;4(7):808-13
references.pmid: 9662372
references.citation: Am J Ophthalmol. 2008 Aug;146(2):292-7
references.pmid: 18547534
references.citation: Hum Immunol. 2002 Jun;63(6):435-43
references.pmid: 12039518
references.citation: Br J Ophthalmol. 1987 Nov;71(11):844-9
references.pmid: 3689736
references.citation: Cancer Immunol Immunother. 2000 Sep;49(7):361-8
references.pmid: 10999462
references.citation: Invest Ophthalmol Vis Sci. 1991 Jul;32(8):2201-11
references.pmid: 2071334