Mucosal-associated invariant T cells are reduced and functionally immature in the peripheral blood of primary Sjögren's syndrome patients

Abstract

The frequencies, immunophenotype, and function of mucosal-associated invariant T (MAIT) cells were studied in patients with primary Sjögren syndrome (pSS) and healthy controls. MAIT cells were significantly decreased in the peripheral blood (PB) of patients with pSS. Vα7.2+ MAIT cells were detected in the salivary gland tissue from pSS patients, but not in controls, indicating that the reduction of MAIT cells in PB might be due to migration into the target tissue. Furthermore, the residual peripheral blood MAIT cells in pSS patients showed altered immunophenotype and function. While MAIT cells from controls were almost exclusively CD8+ and expressed an effector memory immunophenotype, in pSS patients they were enriched in CD4+ and naïve subpopulations. Consistently, the functional studies demonstrated that MAIT cells from pSS showed a lower level of activation with reduced expression of CD69 and CD154 (CD40L), and a lower production of TNF and IFN-γ. In summary, our findings demonstrate that MAIT cells were reduced and phenotypically and functionally altered in PB of pSS patients. The altered function of MAIT cells in target tissues from pSS patients may result in dysregulation of mucosal immunity leading to microbial damage of mucosal surfaces and subsequent initiation of autoimmune response.