Recruitment of circulating antigen presenting cells to the retina is necessary for induction of autoimmune retinitis

Abstract BackgroundCharacterizing 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.R3 background), which spontaneously and rapidly develop severe autoimmune retinitis (AR), were crossed to CD11cDTR/GFP mice (B6/J) allowing us to track the recruitment to and/or expansion within the retina of activated, antigen presenting cells (GFPhi cells) in R161H+/- x CD11cDTR/GFP F1 mice relative to the course of AR. Parabiosis between R161H+/- x CD11cDTR/GFP F1 mice and B10.R3 x 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 AR in R161H+/- x CD11cDTR/GFP F1 mice was delayed relative to B10.R3-R161H+/- mice revealing a disease prophase prior to frank autoimmunity that was characterized by expansion of GFPhi cells within the retina prior to any clinical or histological evidence of autoimmunity. Parabiosis between mice carrying the R161H and CD11cDTR/GFP transgenes and transgene negative recipients showed that recruitment of circulating GFPhi cells to retinas was required for induction of AR. ConclusionsOur results here contrast with our previous findings showing that retinal antigen presenting cells expanding in response to either sterile inflammatory injury or neurodegeneration were derived from myeloid cells within the retina or optic nerve thus highlighting a unique facet of retinal autoimmunity.