Tertiary lymphoid tissue with germinal centers and T follicular helper cells in immunologically privileged retinas of mice with chronic autoimmune uveitis (P4172)

Abstract

Abstract Mice transgenic for a retina-specific T cell receptor develop spontaneous autoimmune uveitis. In contrast to induced models of uveitis the disease is prolonged and the mice display distinct retinal lesions that resemble tertiary lymphoid tissue. Here we investigate these lesions for presence of germinal center (GC) and T follicular helper cell (TfH) markers. Retinas were immunohistochemically stained for CD4+ T cells, CD8+ T cells, and B cells, as well as the GC markers PNA and GL-7. The retinal lesions stained positively for CD4+ T cells and B cells and also for PNA and GL-7. Laser capture microdissection was then used to isolate the retinal lesions and microarray analysis was performed to assess expression of GC- and TfH-associated genes. The microdissected lesions consistently showed upregulation of germinal center markers and T follicular helper cell markers with a 4 fold increase in Btla, Fas, and CXCL13, a 3.5 fold increase in CXCR5, and a doubling in CXCR4 compared to control retina. Heat map analysis revealed a similar gene expression profile of the retinal lesions to that of germinal centers present in 5 day-immunized spleen and lymph nodes. We conclude that despite the immunologically privileged status enjoyed by the eye, chronic autoimmune uveitis precipitates development of tertiary lymphoid tissue in the retina, expressing genes and immunological markers characteristic of GC and TfH.