Background/Purpose:

Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that express a semi-invariant TCRα chain: Vα7.2-Jα33 in humans and Vα19-Jα33 in mice. MAIT cells are restricted by the MHC-related molecule-1 (MR1) and uniquely recognize microbial-derived vitamin B metabolites presented by MR1. Like other innate-like lymphocytes, MAIT cells are also activated by cytokines in the absence of exogenous antigens. Human MAIT cells are abundant and constitute approximately 5% of peripheral blood T cells, suggesting possible roles of MAIT cells in various types of immune responses. Previously we demonstrated that the frequency of MAIT cells was markedly reduced in patients with systemic lupus erythematous (SLE). In this study, we aimed to investigate whether MAIT cells are involved in the pathogenesis of SLE.

Methods:

Peripheral blood was collected from SLE patients and healthy volunteers. Informed consent was obtained from all individuals according to institutional ethical guidelines. Disease activity was measured based on the SLE disease activity index (SLEDAI) and a SLEDAI score ≥ 5 was defined as active disease. Peripheral blood mononuclear cells (PBMC) were stained with anti-human monoclonal antibodies against CD3, γδTCR, Vα7.2TCR, CD161, CD95(Fas) and CD69, and then analyzed by FACS. The activation status of MAIT cells was assessed by the expression of CD69. MAIT cells were sorted from PBMC of healthy individuals by using magnetic cell sorting (MACS) and FACS Aria. CD19⁺B cells or CD14⁺monocytes were isolated from PBMC of healthy controls (HC) or SLE patients by using MACS. MAIT cells were co-cultured with B cells or monocytes in the presence of MR1 ligand (MR1L), and the expression of CD69 on MAIT cells was evaluated by FACS. Cytokine levels in plasma samples and culture supernatants were measured by ELISA and Bioplex assay. PBMC were cultured in the presence of various cytokines, and CD69 expression on MAIT cells was analyzed by FACS.

Results:

 MAIT cells from lupus patients with active disease expressed high levels of CD69, a lymphocyte activation marker, and the frequency of CD69⁺MAIT cells positively correlated with SLEDAI. MAIT cells cultured with lupus monocytes displayed higher levels of CD69 compared with cells cultured with monocytes from healthy controls. The profound MAIT cell activating capacity of lupus monocytes was associated with enhanced IL-12 production in the culture supernatants.The plasma levels of cytokines including IL-6, IL-18 and IFNα positively correlated with the expression levels of CD69 on MAIT cells. MAIT cells were activated by cytokines including IFNα, IL-15, and IL-12 plus IL-18 in the absence of exogenous antigens.

Conclusion:

The activated state of MAIT cells sensitively reflected disease activity of SLE. We revealed two possible mechanisms of MAIT cell activation in SLE. First, we demonstrated that lupus monocytes displayed a profound MAIT cell activation capacity. Second, we found that the elevated levels of IL-18 and IFNα correlated with the activate state of MAIT cells in SLE, and this may elicit the cytokine-mediated activation of these cells. Because these cytokines have been suggested to be involved in the pathogenesis of SLE, activated MAIT cells may play an important in lupus pathology.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/activation-status-of-mucosal-associated-invariant-t-cells-sensitively-reflects-disease-activity-of-systemic-lupus-erythematosus/