Immunology of the eye
Methods We performed RNA and TCR sequencing on aqueous fluid and peripheral blood obtained from a 67-year-old female with active chronic granulomatous anterior uveitis, suspected to be sarcoidosis.
Results The ocular inflammatory cells included 4 major cell types. CD4+ T cells comprised 48% of the sample, CD8+ T cells 18%, B cells 26% and monocytes 8%. The CD4:CD8 T cell ratio was 2.7. Pathway analysis revealed upregulation of types I and II interferon (IFN) as well as TNFa, but not of IL-17 signaling.
Clonal TCR sequences were found among CD4+ but not CD8+ T cells. The five most frequent clones represented 25% of all TCRs. Notably, these clones were not detected in the patient’s peripheral blood.
While a subset of the ocular CD4+ T cells had a similar phenotype to circulating peripheral memory T cells, most had increased expression of effector molecules including IFN g, granzyme and perforin molecules. Notably, the dominant TCR clones were found amongst these effector cells.
Most ocular B cells had a class-switched memory phenotype, without evidence of monoclonality and expressed MHC II, T cell costimulatory CD40 and CD86, and toll-like-receptors (TLRs). Additionally, 19% of the B cells were plasmablasts.
These data suggest a local antigen-driven immune response. Furthermore, the apparent lack of common CD4+ T cells clones in the peripheral blood suggests that the local immune response may be self-perpetuating and may not require distal priming/activation of inflammatory cells. This insight provides the groundwork for enhanced prediction and monitoring of therapeutic responses in uveitis.