Parabiosis reveals the correlation between the recruitment of circulating antigen presenting cells to the retina and the induction of spontaneous autoimmune uveoretinitis

Abstract

AbstractBackgroundCharacterizing immune cells and conditions that govern their recruitment and function in autoimmune diseases of the nervous system or in neurodegenerative processes is an area of active investigation. We sought to analyze the origin of antigen presenting cells associated with the induction of retinal autoimmunity using a system that relies on spontaneous autoimmunity, thus avoiding uncertainties associated with immunization with adjuvants at remotes sites or adoptive transfer of in vitro activated T cells.MethodsR161H mice (B10.RIII background), which spontaneously and rapidly develop severe spontaneous autoimmune uveoretinitis (SAU), were crossed to CD11cDTR/GFPmice (B6/J) allowing us to track the recruitment to and/or expansion within the retina of activated, antigen presenting cells (GFPhicells) in R161H+/− × CD11cDTR/GFPF1mice relative to the course of SAU. Parabiosis between R161H+/− × CD11cDTR/GFPF1mice and B10.RIII × B6/J F1(wild-type recipient) mice was done to explore the origin and phenotype of antigen presenting cells crucial for the induction of autoimmunity. Analysis was done by retinal imaging, flow cytometry, and histology.ResultsOnset of SAU in R161H+/− × CD11cDTR/GFPF1mice was delayed relative to B10.RIII-R161H+/−mice revealing a disease prophase prior to frank autoimmunity that was characterized by expansion of GFPhicells within the retina prior to any clinical or histological evidence of autoimmunity. Parabiosis between mice carrying the R161H and CD11cDTR/GFPtransgenes and transgene negative recipients showed that recruitment of circulating GFPhicells into retinas was highly correlative with the occurrence of SAU.ConclusionsOur results here contrast with our previous findings showing that retinal antigen presenting cells expanding in response to either sterile mechanical injury or neurodegeneration were derived from myeloid cells within the retina or optic nerve, thus highlighting a unique facet of retinal autoimmunity.