Session Title: T Cell Biology and Targets in Autoimmune Disease Poster II
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
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.
To cite this abstract in AMA style:Joachims ML, Lawrence C, Pelikan RC, Leehan KM, Radfar L, Lewis DM, Rasmussen A, Scofield RH, Grundahl K, Sivils KL, Thompson LF, Farris AD. Single Cell Analysis of TCRs from CD8+ T Cells in Sjogren’s Syndrome [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/single-cell-analysis-of-tcrs-from-cd8-t-cells-in-sjogrens-syndrome/. Accessed December 4, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/single-cell-analysis-of-tcrs-from-cd8-t-cells-in-sjogrens-syndrome/