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 have been suggested to play both proinflammatory and regulatory roles in autoimmune models. Although MAIT cells are rare in mice, human MAIT cells are more abundant and constitute approximately 5% of peripheral blood T cells, suggesting possible roles of MAIT cells in human autoimmune diseases. Previously we demonstrated that MAIT cells underwent activation-induced cell death and their frequency was markedly reduced in patients with systemic lupus erythematous (SLE). In this study, we aimed to investigate the mechanism by which MAIT cells are activated in SLE.

Methods: Peripheral blood was collected from SLE patients and healthy volunteers. Informed consent was obtained from all individuals according to institutional ethical guidelines. Peripheral blood mononuclear cells (PBMC) of SLE patients as well as healthy volunteers were stained with anti-human monoclonal antibodies against CD3, γδTCR, Vα7.2TCR, CD161, and CD69. MAIT cells were identified as CD3⁺gdTCR^–Va7.2TCR⁺CD161^high cells by flow cytometetry. 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 stimulated with MR1L was evaluated by FACS. The serum cytokine levels were measured by ELISA or magnetic bead-based assays. 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. Although B cells from SLE patients and healthy controls equally activated MAIT cells in the presence of MR1L, the activation capacity of lupus monocytes was greatly augmented compared to healthy controls. The serum levels of cytokines including IL-12 and IL-18 were increased in active SLE and MAIT cells were activated by cytokines in the absence of exogenous antigens in vitro.

Conclusion: Monocytes and inflammatory cytokines may contribute to the hyperactivated state of MAIT cells in SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hyperactivated-state-of-mucosal-associated-invariant-t-cells-due-to-activation-potency-of-monocytes-in-systemic-lupus-erythematous/