TY - JOUR
T1 - Spontaneous Ocular Autoimmunity in Mice Expressing a Transgenic T Cell Receptor Specific to Retina
T2 - A Tool to Dissect Mechanisms of Uveitis
AU - Horai, R.
AU - Chong, W.P.
AU - Zhou, R.
AU - Chen, J.
AU - Silver, P.B.
AU - Agarwal, R.K.
AU - Caspi, R.R.
N1 - Funding information:
The authors thank the NEI Genetic Engineering Core for assistance in generating the R161 TCR mouse strains. This study was supported by NIH/NEI Intramural funding, Project # EY000184.
Publisher copyright:
© 2015 Bentham Science Publishers
PY - 2015/8
Y1 - 2015/8
N2 - The “classical” EAU model induced by immunization of mice with the retinal protein IRBP or its peptides has been very useful to study basic mechanisms of ocular inflammation, but is inadequate for some types of studies due to the need for active immunization in the context of strong bacterial adjuvants. We generated transgenic (Tg) mice on the B10.RIII background that express a T cell receptor (TCR) specific for IRBP161-180. Three strains of TCR Tg mice were established. Spontaneous uveitis developed in two of the three strains by 2-3 months of age. Susceptibility correlated with a higher copy number of the transgenic TCR and a higher proportion of TCR Tg T cells in the peripheral repertoire. Even in mice with uveitis, peripheral IRBP-specific CD4+ T cells displayed mostly a naïve phenotype. In contrast, T cells infiltrating uveitic eyes mostly showed an effector/memory phenotype, and included Th1, Th17 as well as T regulatory cells. These mice thus provide a new and distinct model of uveitis from the “classical” EAU, and may represent some types of uveitis more faithfully. Importantly, this new transgenic model of uveitis can serve as a template for therapeutic manipulations, and as a source of naïve retina-specific T cells for a variety of basic and pre-clinical studies. Several examples of such studies will be discussed.
AB - The “classical” EAU model induced by immunization of mice with the retinal protein IRBP or its peptides has been very useful to study basic mechanisms of ocular inflammation, but is inadequate for some types of studies due to the need for active immunization in the context of strong bacterial adjuvants. We generated transgenic (Tg) mice on the B10.RIII background that express a T cell receptor (TCR) specific for IRBP161-180. Three strains of TCR Tg mice were established. Spontaneous uveitis developed in two of the three strains by 2-3 months of age. Susceptibility correlated with a higher copy number of the transgenic TCR and a higher proportion of TCR Tg T cells in the peripheral repertoire. Even in mice with uveitis, peripheral IRBP-specific CD4+ T cells displayed mostly a naïve phenotype. In contrast, T cells infiltrating uveitic eyes mostly showed an effector/memory phenotype, and included Th1, Th17 as well as T regulatory cells. These mice thus provide a new and distinct model of uveitis from the “classical” EAU, and may represent some types of uveitis more faithfully. Importantly, this new transgenic model of uveitis can serve as a template for therapeutic manipulations, and as a source of naïve retina-specific T cells for a variety of basic and pre-clinical studies. Several examples of such studies will be discussed.
KW - Autoimmunity
KW - uveitis
KW - EAU
KW - Animal model
KW - Th1
KW - Th17
UR - http://europepmc.org/abstract/med/26238373
UR - https://www.scopus.com/inward/record.uri?eid=2-s2.0-84940935601&doi=10.2174%2f1566524015666150731095201&partnerID=40&md5=cc951dec01d0c917538137f22119e0a9
U2 - 10.2174/1566524015666150731095201
DO - 10.2174/1566524015666150731095201
M3 - Journal article
C2 - 26238373
SN - 1566-5240
VL - 15
SP - 511
EP - 516
JO - Current Molecular Medicine
JF - Current Molecular Medicine
IS - 6
ER -
