Abstract
Purpose: :
T cells recognizing central nervous system antigens can elicit autoimmune disease or sometimes mediate neuroprotection ("beneficial autoimmunity"). However, these studies were done with polyclonal T cells that had to be previously activated and/or cultured. To more closely mimic a natural situation, we determined whether naïve retina-specific GFP+ T cells have the ability to migrate to eyes of mice subjected to optic nerve crush injury.
Methods: :
B10.R111 mice 10-14 weeks of age underwent fluorogold labeling of retinal ganglion cells in the superior colliculus. The mice then received an adoptive transfer of 2 million R161h GFP+ lymphocytes from transgenic mice (R161H) that express a retina specific T cell receptor and spontaneously develop uveitis. Immediately after adoptive transfer, mice were subjected to optic nerve crush injury in one eye. Mice were sacrificed 4 days or 1 week post optic nerve crush injury. Retinas were flatmounted for confocal microscopy image analysis. A total of 20 fields per eye were collected and retinal ganglion cells were counted in each field and averaged. Eyes at each timepoint were also cryosectioned and imaged to examine the presence and localization of R161 GFP+ cells in optic nerve injured mice.
Results: :
Approximately 20% ganglion cell loss was observed at 4 days and 70% at 7 days post optic nerve crush in the injured eye compared to the control uninjured eye. At both these time points GFP+ R161H autoreactive cells could be observed in the optic nerve head of injured, but not uninjured eyes.
Conclusions: :
Autoreactive GFP+ cells are recruited into eyes of optic nerve injured mice. Their presence could affect the rate of retinal ganglion cell loss early in optic nerve injury.
Keywords: immunomodulation/immunoregulation • optic nerve • neuroprotection