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OP0214 Activation status of mucosal-associated invariant t cells reflects pathology of systemic lupus erythematosus
  1. A Chiba1,
  2. G Murayama1,2,
  3. N Tamura2,
  4. K Yamaji2,
  5. Y Takasaki2,
  6. S Miyake1
  1. 1Immunology
  2. 2Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan

Abstract

Background Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that express a semi-invariant TCRα chain (Vα7.2-Jα33 in humans). MAIT cells are restricted by the MHC-related molecule-1 (MR1) and uniquely recognize 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.

Objectives We aimed to investigate whether MAIT cells are involved in systemic lupus erythematous (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. CD19+B cells or CD14+monocytes were isolated from PBMC of healthy controls (HC) or SLE patients by using magnetic cell sorting. MAIT cells from healthy controls 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 The frequency of MAIT cells was markedly reduced in SLE. Reduced numbers of MAIT cells were not attributable to the downregulation of surface markers, but were partially due to the enhanced cell death of MAIT cells, possibly by activation-induced cell death. The CD69 expression levels on MAIT cells in SLE correlated with disease activity. Monocytes from patients with SLE exhibited increased ability to induce MAIT cell activation, and the profound MAIT cell activating capacity of lupus monocytes was associated with enhanced IL-12 production in the culture supernatants. The plasma concentration of IL-6, IL-18 and IFNα positively correlated with the expression levels of CD69 on MAIT cells in SLE. MAIT cells were activated by cytokines including IFNα, IL-15, and IL-12 plus IL-18 in the absence of exogenous antigens.

Conclusions These results suggest that MAIT cells reflect the pathological condition of SLE and their activated status correlates with disease activity.

References

  1. Miyazaki Y, et al. Mucosal-associated invariant T cells regulate Th1 response in multiple sclerosis. Int. Immunol. 2011;23:529–35.

  2. Chiba A, et al. Mucosal-associated invariant T cells promote inflammation and exacerbate disease in murine models of arthritis. Arthritis Rheum. 2012; 64:153–61.

  3. Hayashi E, et al. Involvement of Mucosal-associated Invariant T cells in Ankylosing Spondylitis. J Rheumatol. 2016; 43: 1695–703.

References

Disclosure of Interest None declared

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