AxSpA joint tissue is characterised by HLA-DR ⁺ tissue resident memory (TRM) and killer cell immunoglobulin-like receptor (KIR) ⁺ CD8 ⁺ T cell subsets

Axial Spondyloarthritis (AxSpA) is a common inflammatory arthritis with HLA-B*27 as the major genetic risk. Recent discoveries of AxSpA-specific T cell receptor (TCR) motifs and the self and bacterial peptides that they recognize support a pathogenic role of CD8 ⁺ T cells. Despite of previous work on synovial fluid, the characteristics of CD8 cells in joint tissue are currently unknown.

Method

Synovial tissues from 5 AxSpA patients were used for single cell RNA sequencing (scRNA-seq). Paired TCR sequencing was carried out for 2. The abundance of KIR ⁺ CD8 ⁺ T cells in the blood from 9 AxSpA patients and 10 healthy controls was measured using flow cytometry. The expression of naïve and memory T cell markers (CCR7, CD45RA and CD45RO) were compared between KIR ⁺ and KIR ^- CD8 cells.

Results

We observed conventional, TRAV1-2 ⁺ mucosal-associated invariant T (MAIT) cell and MKI67 ⁺ proliferating cell populations in synovium. Following sub-clustering of conventional CD8 ⁺ T cells, HLA-DR ⁺ tissue resident memory (TRM), circulating, KIR ⁺ and FCGR3A ⁺ (encoding CD16) cell subsets were observed. HLA-DR ⁺ TRM and KIR ⁺ cells were clonally expanded and exhibited distinct transcriptional features, enriched for T cell activation pathways and natural killer (NK) cell-mediated cytotoxicity pathway respectively. Lastly, KIR ⁺ CD8 ⁺ T cells were increased in AxSpA blood and enriched for CD45RA ⁺ CCR7 ^- T _EMRA cells.

Conclusion

Here we present the very first transcriptomic profiling of CD8 ⁺ T cells in synovium tissue and highlight potential roles of HLA-DR ⁺ TRM and KIR ⁺ cells in AxSpA pathology. This study adds novel insights to the disease mechanisms and offers new therapeutic opportunities.