Expansions of Salivary Gland CD4+ T Cells from Sjögren's Syndrome Patients: Single-Cell Repertoire Analysis and Correlation with Clinical Measures of Disease

Michelle L. Joachims¹, Kerry M. Leehan^2,3, Christina M. Lawrence³, Astrid Rasmussen³, Lida Radfar⁴, David M. Lewis⁵, Glen D Houston⁶, Kiely Grundahl³, Donald U. Stone^7,8, Kimberly Hefner⁹, R. Hal Scofield^2,10,11, Kathy L. Sivils^2,3, Linda F. Thompson¹² and A. Darise Farris^1,2, ¹Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, ²Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, ³Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, ⁴Oral Diagnosis and Radiology Department, University of Oklahoma Health Sciences Center College of Dentistry, Oklahoma City, OK, ⁵College of Dentistry, Department of Oral and Maxillofacial Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, ⁶Heartland Pathology, Oklahoma City, OK, ⁷Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, ⁸King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, ⁹Hefner Eye Care and Optical Center, Oklahoma City, OK, ¹⁰College of Medicine, Section of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, OK, ¹¹Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹²Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Sjogren's syndrome, T cells and salivary gland

Session Information

Date: Sunday, November 8, 2015

Title: Sjögren's Syndrome I: Basic Insights

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: CD4⁺ T cells predominate in salivary gland (SG) focal lymphocytic infiltrates in primary Sjögren’s syndrome (pSS). However, their antigen specificity, degree of clonal expansion and relationship to clinical disease features remain unknown. Here, we determined the T cell receptor (TCR) repertoire of CD4⁺memory T cells in SG and peripheral blood (PB) of pSS patients and assessed whether the frequencies of clonally expanded SG T cells correlate with specific measures of disease.

Methods: Multiplex single cell RT-PCR was used to amplify both the α and β TCR sequences from individual memory CD4⁺T cells sorted from SG lip biopsy tissue and PB of 10 patients fulfilling both the 2002 Revised American European Consensus Group Criteria and the 2012 Provisional ACR Criteria for pSS. Percentages of T cells that were part of SG clonal expansions were calculated and correlated with various measures of disease.

Results: Over 3,000 TCR sequences were obtained from 50-115 (median 91) individual SG and 75-121 (median 108) individual PB CD4⁺ memory T cells per patient. The percentages of cells that were part of clonal expansions were significantly higher in SG (median 12%, range 0-28%) compared to PB (median 0.9%, range 0-7%, p=0.002). The TCR sequences of expanded memory CD4⁺T cells in SG were largely distinct from those in PB and were enriched for cells expressing dual productive TCRα transcripts (χ2=4.42, p=0.036). Sequence analysis revealed: 1) highly homologous CDR3s among different expanded SG T cell clones within single patients, suggesting antigen-driven expansion and 2) unique cases of convergent recombination among unrelated patients, where different V segments/additions/deletions were utilized to make identical CDR3 amino acid sequences. The percentages of clonally expanded CD4⁺memory T cells in SG correlated significantly with reduced whole unstimulated salivary flow (r=-0.758, p=0.015) and increased degree of SG fibrosis (r=0.661, p=0.044) but not with systemic features of disease.

Conclusion: SG clonal expansions detected in this study likely identify T cells involved in recognition of common antigen(s) and glandular dysfunction.

Disclosure: M. L. Joachims, None; K. M. Leehan, None; C. M. Lawrence, None; A. Rasmussen, None; L. Radfar, None; D. M. Lewis, None; G. D. Houston, None; K. Grundahl, None; D. U. Stone, None; K. Hefner, None; R. H. Scofield, None; K. L. Sivils, None; L. F. Thompson, None; A. D. Farris, None.

To cite this abstract in AMA style:

Joachims ML, Leehan KM, Lawrence CM, Rasmussen A, Radfar L, Lewis DM, Houston GD, Grundahl K, Stone DU, Hefner K, Scofield RH, Sivils KL, Thompson LF, Farris AD. Expansions of Salivary Gland CD4+ T Cells from Sjögren’s Syndrome Patients: Single-Cell Repertoire Analysis and Correlation with Clinical Measures of Disease [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/expansions-of-salivary-gland-cd4-t-cells-from-sjogrens-syndrome-patients-single-cell-repertoire-analysis-and-correlation-with-clinical-measures-of-disease/. Accessed .

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