The eye's view of antigen presentation.
A form of systemic tolerance is created when antigenic material is placed in the anterior chamber of the eye, an immune privileged site. Termed anterior chamber associated immune deviation (ACAID), this form of tolerance insures that the systemic immune response to eye-derived antigens is devoid of T cells that mediate delayed hypersensitivity and antibodies that fix complement. As a consequence, the eye is spared the disruptive blinding influence of immunogenic inflammation. ACAID arises when antigen is captured by intraocular antigen presenting cells, then carried to the marginal zone of the spleen where, in the presence of natural killer T cells and marginal zone B cells, a microenvironment is created that activates antigen-specific T cells to differentiate into regulatory cells that interfere with the induction of delayed hypersensitivity as well as its expression. Transforming growth factor beta-2 (TGFbeta-2), constitutively present in the aqueous humor of the eye, imposes distinctive properties on antigen presenting cells. Thrombospondin is an early activated gene following TGFbeta-2 treatment and as a consequence the eye-derived antigen presenting cells fail to secrete IL-12 or express CD40. The lack of these potent stimulators of Th1 cell differentiation is central to the induction of ACAID.
Streilein
J Wayne
JW
Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA. waynes@vision.eri.harvard.edu
Masli
Sharmila
S
Takeuchi
Masaru
M
Kezuka
Takeshi
T
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000378:metabolism; D015551:Autoimmunity; D002490:Central Nervous System / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D005123:Eye / Q000276:immunology*; D007108:Immune Tolerance; D018448:Models, Immunological; D009928:Organ Specificity; D013154:Spleen / Q000276:immunology; D019700:Thrombospondin 1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; D003165:Complement System Proteins