Analysis of CD4 T cells in granulomatous uveitis (GU) with single-cell RNA sequencing (scRNAseq)
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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
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