Abstract
| Original language | English |
|---|---|
| Article number | 14226 |
| Number of pages | 13 |
| Journal | Scientific Reports |
| Volume | 7 |
| DOIs | |
| Publication status | Published - 27 Oct 2017 |
Keywords
- autoimmunity
- inflammation
Cite this
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Ocular antigen does not cause disease unless presented in the context of inflammation. / Voigt, Valentina; Wikstrom, Matthew E.; Kezic, Jelena M.; Schuster, Iona S.; Fleming, Peter; Makinen, Kimmo; Daley, Stephen R.; Andoniou, Christopher E.; Degli-Esposti, Mariapia A.; Forrester, John V.
In: Scientific Reports, Vol. 7, 14226, 27.10.2017.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Ocular antigen does not cause disease unless presented in the context of inflammation
AU - Voigt, Valentina
AU - Wikstrom, Matthew E.
AU - Kezic, Jelena M.
AU - Schuster, Iona S.
AU - Fleming, Peter
AU - Makinen, Kimmo
AU - Daley, Stephen R.
AU - Andoniou, Christopher E.
AU - Degli-Esposti, Mariapia A.
AU - Forrester, John V.
PY - 2017/10/27
Y1 - 2017/10/27
N2 - 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.
AB - 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.
KW - autoimmunity
KW - inflammation
U2 - 10.1038/s41598-017-14618-z
DO - 10.1038/s41598-017-14618-z
M3 - Article
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 14226
ER -