Tissue resident memory T cells populate the human uveal tract

Area of Science:

• Immunology
• Ophthalmology
• Cell Biology

Background:

• The eye is traditionally considered an immune-privileged site.
• Resident T cells are known to drive inflammatory diseases in other tissues.
• The role of intraocular T cells in non-infectious uveitis is not well understood.

Purpose of the Study:

• To investigate the presence and function of resident T cells within the human eye.
• To determine the involvement of T cells, particularly tissue-resident memory T (T_RM) cells, in non-infectious immune-mediated uveitis.

Main Methods:

• Spectral cytometry and immunofluorescence imaging of uveal tissue.
• Single-cell RNA and T cell receptor (TCR) sequencing of aqueous humor.
• Bulk RNA sequencing and weighted gene co-expression network analysis (WGCNA).
• Studies in mouse models of experimental autoimmune uveoretinitis (EAU).

Main Results:

• Non-inflamed human uveal tissue harbors diverse T cell subtypes, including CD8+CD103+ T_RM cells.
• Active uveitis involves clonally expanded T cells enriched for T_RM-associated genes in the aqueous humor.
• CD8+CD103+ T cells persist in the uveal tract during active human uveitis.
• Quiescent iris tissue from uveitis patients shows enrichment for T cell activation and antigen presentation genes.
• T_RM cells persist in the anterior uvea of mice after EAU resolution.

Conclusions:

• The human eye contains resident T cells in both healthy and inflamed states, challenging previous dogma.
• Resident T cells, particularly T_RM cells, are involved in the pathogenesis of non-infectious immune-mediated uveitis.
• Intraocular resident T cells represent promising therapeutic targets for uveitis treatment.