Category: 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.
Lynn Hassman– Assistant Professor, Washington University in St. Louis
Michael Paley– Instructor, Washington University in St. Louis
Ekaterina Esaulova– graduate student, Washington University in St. Louis
Wayne Yokoyama– Professor, Washington University in St. Louis