The current paradigm suggests that the uveal tract of the eye is an immune-privileged site and therefore devoid of lymphocytes. There is now accumulating evidence that demonstrates resident T cells occupy intraocular tissues. In immune-mediated inflammatory diseases such as psoriasis and rheumatoid arthritis, tissue resident T cells trigger disease flares in the skin and joints. This suggests resident T cells in the uvea may have similar functions in non-infectious immune-mediated uveitis, a collective term for autoinflammatory and autoimmune diseases of the uveal tract causing intraocular inflammation.

Here, we demonstrate by spectral cytometry and immunofluorescence imaging that non-inflamed uveal tissue contains multiple T cell subtypes including CD8+ CD103+ tissue resident memory T (TRM) cells. Using single cell RNA & T cell receptor (TCR) sequencing to profile aqueous humour cells from donors with acute, active uveitis, we identify that clonally expanded T cells are enriched for TRM -associated genes. We further show that in donors with active uveitis, CD8+ CD103+ cells persist within the uveal tract. Finally, using bulk RNA sequencing and weighted gene co-expression network analysis (WGCNA) analysis we show that quiescent iris tissue from donors with a history of uveitis are enriched for genes associated with T cell activation and antigen presentation. Our results show that the human eye contains T cells both in health and during active inflammation. Our findings challenge the dogma that the eye is devoid of lymphocytes and supports the concept of resident T cell involvement in the pathogenesis of non-infectious immune-mediated uveitis.