Background/Purpose: Sjögren’s syndrome (SS) is an autoimmune exocrinopathy characterized by focal lymphocytic infiltration of the salivary and lacrimal glands, severe dry eyes and mouth, fatigue and musculoskeletal pain. How the T cell-dominated salivary gland (SG) inflammation is connected to pathologic and clinical features of SS is poorly understood. We reported that SG CD4⁺ T cell clonal expansion is antigen-driven and correlated with reduced salivary flow and increased SG fibrosis. To determine whether the extent of SG CD8⁺ T cell clonal expansion is related to pathologic features of disease, we evaluated the CD8⁺ TCR repertoire of the same subjects.

Methods: Multiplex single cell RT-PCR was used to retrieve paired TCR α and β sequences from SG and peripheral blood (PB) memory CD8⁺ T cells from 11 subjects meeting the 2016 ACR/EULAR classification criteria for primary Sjögren’s syndrome. The extent of SG and PB CD8⁺ T cell clonal expansion was compared between SG and PB and evaluated for relationships with pathologic and clinical disease features using Mann-Whitney and Spearman rank correlation tests.

Results: Our cohort repertoire consisted of over 2,800 TCR sequences isolated from a median of 28 (range 4-67) SG and 19 (range 4-52) PB cells evaluated per subject. Clonal expansions of SG and PB CD8⁺ T cells were detected in all subjects. Expansions were extensive in both tissue compartments, ranging from 8.3-66.3% in SG (mean 34.9) and 5-48.5% in PB (mean 23.1). Although the percentage of clonally expanded CD8⁺ T cells did not differ significantly between SG and PB, there were significantly higher levels of clonally expanded SG CD8⁺ T cells compared to SG CD4⁺ T cells from the same individuals. Further, many subjects exhibited large expansions, with 60% of individuals having at least one clonal expansion of 4 or more cells. In contrast to our prior observations in CD4⁺ T cells, the degree of SG CD8⁺ T cell clonal expansion did not significantly correlate with measures of oral disease. However, identical clonal expansions were detected in SG and PB in 5/11 patients (45%), indicating significant trafficking of CD8⁺ T cells in both tissues. Further, several clonotypes of expanded cells shared between SG and PB were identified as viral-specific, indicating the presence of activated viral-specific T cells in the SG of SS patients.

Conclusion: Although relatively small numbers of T cells were evaluated in this study, clonally expanded CD8⁺ T cells were abundant in both the SG and PB of SS patients but did not obviously correlate with measures of disease. Known viral-specific T cells were found in SG and PB from SS patients, adding evidence for viral-initiated or -driven CD8⁺ T cell proliferation in SS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/single-cell-analysis-of-tcrs-from-cd8-t-cells-in-sjogrens-syndrome/