| Presentation preference | Oral presentation |
| Title | Analysis of CD4 T cells in granulomatous uveitis (GU) with single-cell RNA sequencing (scRNAseq) |
| Accept poster if oral is not possible ? | Yes |
| Purpose | GU is characterized by a CD4 T cell predominant ocular infiltrate, with evidence of oligoclonal antigen specificity in the case of Vogt-Koyanagi-Harada. However, the long-term in vitro culture required to generate these data may have skewed outcomes. |
| Methods | Since scRNAseq provides an unbiased gene expression survey, we used it without in vitro culture to analyze the ocular infiltrate of a subject with chronic granulomatous anterior uveitis. |
| Results | Similar to prior analysis, a plurality of cells was CD4 T cells (48%), with smaller contributions from B cells, CD8 T cells and monocytes. viSNE analysis separated CD4 T cells into 4 transcriptional clusters, including 3 effector/effector-memory clusters characterized by IFN-g, TNF-a, perforin, and granzyme expression. These cytokines were bioactive, indicated by expression of transcripts induced by cytokine signaling. Paired single cell T cell receptor sequencing analysis demonstrated the top 5 most frequent clonotypes comprised more than 25% of all T cells and were restricted to the effector CD4 T cell clusters. However, analysis of the patient’s peripheral blood CD4 T cells did not capture any of these clonotypes, consistent with a tissue-resident response in the eye. |
| Conclusion | Collectively, these data suggest a local, antigen-driven TH1 cell response in chronic GU. Moreover, these TH1 cells appear to be cytolytic, based on their expression of perforin and granzymes, a feature described in other autoimmune diseases. Further investigation of this CD4 T cell response may provide specific targets for therapy. |
| Conflict of interest | No |
Author 1
| Last name | PALEY |
| Initials of first name(s) | M |
| City | St Louis |
| Country | United States |
Author 2
| Last name | Hassman |
| Initials of first name(s) | L |
| City | STL |
| Country | United States |
Author 3
| Last name | Esaulova |
| Initials of first name(s) | E |
| City | STL |
| Country | United States |
Author 4
| Last name | Paley |
| Initials of first name(s) | G |
| City | STL |
| Country | United States |
Author 5
| Last name | Arytomov |
| Initials of first name(s) | M |
| City | STL |
| Country | United States |
Author 6
| Last name | Yokoyama |
| Initials of first name(s) | W |
| City | STL |
| Country | United States |
