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

Friday, November 08, 2013 — Poster Session IV
2:00 p.m. – 4:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NEI	IMMUNO-11

Authors

J.L. Kielczewski
R Horai
Y Jittayasothorn
RR Caspi

Abstract

Mice transgenic for a retina-specific T cell receptor develop spontaneous autoimmune uveitis. The disease in these mice is prolonged and the mice display distinct retinal lesions that resemble tertiary lymphoid tissue. We investigated these retinal lesions for the presence of germinal center (GC) and T follicular helper cell (TfH) markers. Retinas (n=6) were immunohistochemically stained for CD4+ 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 used to isolate the distinct retinal lesions and microarray analysis was performed to assess expression of GC- and TfH-associated genes. The microdissected lesions 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 germinal centers present in immunized mouse lymph nodes. We conclude chronic autoimmune uveitis precipitates development of tertiary lymphoid tissue in the retina, expressing genes and immunological markers characteristic of GC and TfH.