Background/Purpose: Primary Sjögren Syndrome (pSS) is characterized by organ-specific autoimmune destruction of salivary and lacrimal glands. Patients typically experience debilitating symptoms of dry mouth and eyes and commonly develop systemic complications including renal tubular acidosis, arthritis, polysynovitis, refractory pulmonary disease, mixed cryoglobulinaemia, polyclonal hypergammaglobulinaemia and lymphoma. The risk of developing lymphoma is 30-40 times higher in patients with pSS compared to the general population. Autoimmune destruction of glandular tissue in pSS is mediated by conventional CD4+ T helper (Th) – cells but little is known about the involvement of non-conventional, innate-like T-cells in this process. Mucosal-Associated Invariant T (MAIT) – cells are a novel sub-population of unconventional T-cells at the frontier between innate and adaptive immunity. They comprise up to 10% of peripheral blood (PB) T-cells in humans. They accumulate primarily in the intestinal lamina propria and are endowed by a “natural memory” phenotype and function. MAIT cells are able to rapidly produce high levels of Th1, Th2 and Th17 cytokines. One of their proposed roles is protection of mucosal surfaces against vitamin B-metabolizing bacteria and yeasts. To our knowledge, the role of MAIT cells in the pathogenesis of primary Sjögren Syndrome (pSS) has not yet been explored.

Methods: We studied the frequencies, immunophenotype and function of MAIT-cells in the PB of patients with pSS (N=50) and healthy control subjects (HC, N= 22) by using 8- colour flow cytometry and in vitro stimulation assays.

Results: We showed that MAIT cells are significantly decreased in patients with pSS. Furthermore, the residual MAIT cells in pSS patients showed altered immunophenotype and function. While in the HC subjects MAIT cells were almost exclusively CD8⁺ and expressed an effector memory immunophenotype, in pSS patients they were enriched in CD4⁺and naïve subpopulations. This is consistent with our functional studies which 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 IFNγ.

Conclusion: We propose that the reduced frequencies and functional immaturity of MAIT cells in patients with pSS, may result in impaired protective mucosal barrier function and dysregulation of mucosal immunity with subsequent microbial damage to mucosal surfaces and initiation of the autoimmune response. A better understanding of the immunophenotype and function of this novel innate-like T-cell subpopulation in patients with pSS is required in order to evaluate their involvement in the evolution of severe mucosal damage and systemic complications in patients suffering from this debilitating disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mucosal-associated-invariant-t-cells-are-decreased-and-functionally-immature-in-peripheral-blood-of-patients-with-primary-sjogren-syndrome/