Sjögren’s Syndrome Minor Salivary Gland CD4⁺ Memory T Cells Associate with Glandular Disease Features and have a Germinal Center T Follicular Helper Transcriptional Profile

• Main Authors: Michelle L. Joachims, Kerry M. Leehan, Mikhail G. Dozmorov, Constantin Georgescu, Zijian Pan, Christina Lawrence, M. Caleb Marlin, Susan Macwana, Astrid Rasmussen, Lida Radfar, David M. Lewis, Donald U. Stone, Kiely Grundahl, R. Hal Scofield, Christopher J. Lessard, Jonathan D. Wren, Linda F. Thompson, Joel M. Guthridge, Kathy L. Sivils, Jacen S. Moore, A. Darise Farris
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Journal of Clinical Medicine
• Subjects: sjögren’s syndrome; salivary gland; T lymphocytes; transcriptome
• Online Access: https://www.mdpi.com/2077-0383/9/7/2164

To assess the types of salivary gland (SG) T cells contributing to Sjögren’s syndrome (SS), we evaluated SG T cell subtypes for association with disease features and compared the SG CD4⁺ memory T cell transcriptomes of subjects with either primary SS (pSS) or non-SS sicca (nSS). SG biopsies were evaluated for proportions and absolute numbers of CD4⁺ and CD8⁺ T cells. SG memory CD4⁺ T cells were evaluated for gene expression by microarray. Differentially-expressed genes were identified, and gene set enrichment and pathways analyses were performed. CD4⁺CD45RA⁻ T cells were increased in pSS compared to nSS subjects (33.2% vs. 22.2%, <i>p</i> < 0.0001), while CD8⁺CD45RA⁻ T cells were decreased (38.5% vs. 46.0%, <i>p</i> = 0.0014). SG fibrosis positively correlated with numbers of memory T cells. Proportions of SG CD4⁺CD45RA⁻ T cells correlated with focus score (r = 0.43, <i>p</i> < 0.0001), corneal damage (r = 0.43, <i>p</i> < 0.0001), and serum Ro antibodies (r = 0.40, <i>p</i> < 0.0001). Differentially-expressed genes in CD4⁺CD45RA⁻ cells indicated a T follicular helper (Tfh) profile, increased homing and increased cellular interactions. Predicted upstream drivers of the Tfh signature included TCR, TNF, TGF-β1, IL-4, and IL-21. In conclusion, the proportions and numbers of SG memory CD4⁺ T cells associate with key SS features, consistent with a central role in disease pathogenesis.