Ocular antigen does not cause disease unless presented in the context of inflammation.

Abstract:

:Ocular antigens are sequestered behind the blood-retina barrier and the ocular environment protects ocular tissues from autoimmune attack. The signals required to activate autoreactive T cells and allow them to cause disease in the eye remain in part unclear. In particular, the consequences of peripheral presentation of ocular antigens are not fully understood. We examined peripheral expression and presentation of ocular neo-self-antigen in transgenic mice expressing hen egg lysozyme (HEL) under a retina-specific promoter. High levels of HEL were expressed in the eye compared to low expression throughout the lymphoid system. Adoptively transferred naïve HEL-specific CD4+ T cells proliferated in the eye draining lymph nodes, but did not induce uveitis. By contrast, systemic infection with a murine cytomegalovirus (MCMV) engineered to express HEL induced extensive proliferation of transferred naïve CD4+ T cells, and significant uveoretinitis. In this model, wild-type MCMV, lacking HEL, did not induce overt uveitis, suggesting that disease is mediated by antigen-specific peripherally activated CD4+ T cells that infiltrate the retina. Our results demonstrate that retinal antigen is presented to T cells in the periphery under physiological conditions. However, when the same antigen is presented during viral infection, antigen-specific T cells access the retina and autoimmune uveitis ensues.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Voigt V,Wikstrom ME,Kezic JM,Schuster IS,Fleming P,Makinen K,Daley SR,Andoniou CE,Degli-Esposti MA,Forrester JV

doi

10.1038/s41598-017-14618-z

subject

Has Abstract

pub_date

2017-10-27 00:00:00

pages

14226

issue

1

issn

2045-2322

pii

10.1038/s41598-017-14618-z

journal_volume

7

pub_type

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