Tissue resident memory T cells populate the human uveal tract
Foers, Andrew D Reekie, Ian R Wickramasinghe, Lakshanie C Ward, Amy Buckley, Thomas Mw Attar, Moustafa Aguilar-Munoa, Soledad Pilapil, Queen Elsayed, Maram Ea Abdalla Pledger, Sam
Foers, Andrew D
Reekie, Ian R
Wickramasinghe, Lakshanie C
Ward, Amy
Buckley, Thomas Mw
Attar, Moustafa
Aguilar-Munoa, Soledad
Pilapil, Queen
Elsayed, Maram Ea Abdalla
Pledger, Sam
Abstract
The current concept is that the eye is an immune privileged site endowed with innate immune regulatory networks to maintain organ function. We now have evidence that 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 (T) cells. Using single cell RNA & T cell receptor (TCR) sequencing to profile aqueous humour cells from donors with acute, active uveitis, we identify clonally expanded T cells which are enriched for T-associated genes. We further show that in donors with active uveitis, CD8 CD103 T cells persist within tissue in the uveal tract. Using bulk RNA sequencing and weighted gene co-expression network analysis (WGCNA) 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. Finally, we demonstrate that T cells persist in the anterior uvea in mice following resolution of experimental autoimmune uveoretinitis (EAU). 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 and as promising targets for therapy.
MIDER Authors
Affiliations
University of Oxford; University of Bristol; Oxford University Hospitals NHS Trus; Sandwell and West Birmingham NHS Trust; et al.
Date
2026-04-03
Type
Article
Subject
Collections
Citation
Foers AD, Reekie IR, Wickramasinghe LC, Ward A, Buckley TM, Attar M, Aguilar-Munoa S, Pilapil Q, Elsayed MEA, Pledger S, Bhalla A, Hedley R, Hill S, Windell D, Barton K, Masood I, Lim KS, Coles MC, Sherlock JP, Dick AD, Coupland SE, Sansom SN, Copland DA, Buckley CD, Sharma SM; ORBIT Consortium. Tissue resident memory T cells populate the human uveal tract. Sci Rep. 2026 Apr 3;16(1):11330. doi: 10.1038/s41598-025-33444-2