Purchase this article with an account.
Jennifer Lee Kielczewski, Reiko Horai, Rachel R Caspi; Retina-specific T cells provide neuroprotection in a model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2430.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
T cells recognizing central nervous system antigens can elicit autoimmune disease, but when properly controlled can mediate neuroprotection (“beneficial autoimmunity”). We examined whether autoreactive T cells that express a T cell antigen receptor (TCR) specific to the retinal antigen IRBP (R161H cells) provide neuroprotection to ganglion cells in a murine glaucoma model of optic nerve crush injury.
Purified CD4+ T cells or bone marrow (BM) cells were obtained from R161H donor mice genetically marked with eGFP. Wild type (WT) recipients of R161H T cells or R161H BM chimeras (or appropriate controls) underwent fluorogold labeling of retinal ganglion cells and were subjected to optic nerve crush in one eye. Mice were sacrificed 4 or 7 days after the optic nerve injury. Flat-mounted retinas were imaged for quantification of retinal ganglion cells. Retinas were also cryosectioned for microscopy analysis of eGFP+ cell localization.
eGFP+ R161H cells were present in the optic nerve head of adoptively transferred mice at 4 days post optic nerve crush injury. These mice experienced 27% less ganglion cell loss compared to mice infused with control polyclonal eGFP+ T cells (p<0.05). In the R161H BM chimeric model, optic nerve crush injured mice experienced a neuroprotective effect at 1 week post injury with a 16% reduction in ganglion cell loss compared to control eGFP+ chimeric mice (p<0.05). There were significantly more eGFP+ cells around the optic nerve head in R161H BM chimeric mice at 1 week after optic nerve injury compared to control eGFP+ wild type BM chimeric mice.
R161H T cells, whether exogenously administered by adoptive transfer, or endogenously developed from transplanted BM, mediate neuroprotection of retinal ganglion cells.
This PDF is available to Subscribers Only