Clinical relevance of RORγ positive and negative subsets of CD161+CD4+ T cells in primary Sjögren's syndrome.

Objective: The relevance of the Th17 pathway in primary SS (pSS) is unclear. Published studies have relied on restimulating circulating CD161 ⁺ T cells in vitro for quantitation of IL-17-producing cells. While CD161 marks all IL-17 ⁺ T cells, it is also expressed by other Th subsets. The aim of this study was to directly analyse retinoic acid receptor-related orphan nuclear receptor (ROR)-γ expressing and non-expressing subsets of CD161 ⁺ T cells to determine the relevance of the Th17 pathway in pSS.
Methods: We quantitated the frequencies of both CD161 ^- and RORγ-expressing T cells by comparative flow cytometry in peripheral blood mononuclear cells from a well-stratified cohort of pSS patients and control subjects. We also analysed the expression of antigen D-related HLA (HLA-DR) and CD161 in labial salivary glands from nine subjects undergoing a diagnostic biopsy.
Results: While the frequencies of both RORγ ⁺ and RORγ ^- subsets of CD161 ⁺ CD4 ⁺ T cells were increased in peripheral blood from pSS patients, the increase in the RORγ ⁺ subset positively correlated with humoral manifestations of the disease (anti-SSA/SSB autoantibodies and hypergammaglobulinaemia), but not with disease activity, and vice versa for the RORγ ^- subset. An increased frequency of HLA-DR ⁺ CD161 ⁺ CD4 ⁺ T cells was observed in labial salivary gland biopsies from pSS patients, suggesting chronic activation of CD161 ⁺ CD4 ⁺ T cells in the target tissue of the disease.
Conclusion: In addition to pointing to CD161 as a marker of a pathogenic subset of CD4 ⁺ T cells in pSS patients, our data indicate that even though the RORγ ⁺ (Th17) CD161 ⁺ subset might contribute to humoral manifestations of the disease, the RORγ ^- (non-Th17) CD161 ⁺ subset is the one associated with disease activity in pSS patients.
(© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)