Sjogren's Syndrome Minor Salivary Gland CD4+Memory T Cells Associate with Glandular Disease Features and Have a Germinal Center T Follicular Helper Transcriptional Profile

To assess the types of salivary gland (SG) T cells contributing to Sjogren'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%,p< 0.0001), while CD8(+)CD45RA(-)T cells were decreased (38.5% vs. 46.0%,p= 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,p< 0.0001), corneal damage (r = 0.43,p< 0.0001), and serum Ro antibodies (r = 0.40,p< 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-beta 1, 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.