EP238

Do resident T cells drive auto-inflammatory acute anterior uveitis?

FOERS Andrew, HEDLEY Robert, REEKIE Ian, WICKRAMSINGHE Lakshanie, BHALLA Ananya, COPLAND Dave, WARD Amy, CHU Colin, COLES Mark, COUPLAND Sarah, DENNISTON Alastair, DICK Andrew, SHERLOCK Jonathan, SHARMA Srilakshmi, BUCKLEY Chris, CONSORTIUM ORBIT

Purpose

Spondyloarthropathies are a group of diseases, including acute anterior uveitis (AAU), in which tissue resident T cells are proposed as critical to disease pathogenesis. However, this view challenges the classical view of the eye as an immune privileged environment. Identification of resident T cells within and surrounding the anterior uvea would support their involvement in AAU pathogenesis.

Methods

To identify T cells, uveas were separated from post-mortem human eyes with no history of eye disease (n=3), dissected into iris, ciliary body and choroid, digested and assessed by scRNAseq and flow cytometry. Spatial location was assessed on formalin-fixed paraffin-embedded eye sections by multiplexed immune-fluorescent imaging on the Cell DIVE platform.

Results

scRNAseq identified discrete T cell clusters within the ciliary body and choroid. These clusters were further characterised by flow cytometry. CD3+, CD69+ and CD45RO+ populations were identified, consistent with a resident memory phenotype. Immune-fluorescent imaging further confirmed the presence of CD3+ cells with a resident phenotype and their localisation outside of CD31+ blood vessels.

Conclusions

In this study, we demonstrate that resident T cells populate the healthy human eye. This challenges the dogma that the eye is devoid of lymphocytes and supports involvement of T cells in the pathogenesis of auto-inflammatory AAU. Further work is planned to investigate what sub-populations of T cells expand in AAU.  

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