Background/Purpose: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes which are restricted by the MHC-related molecule-1 (MR1) and express a semi-invariant TCRα chain: Vα7.2-Jα33 in humans and Vα19-Jα33 in mice. MAIT cells 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 have revealed that the frequency of MAIT cells was reduced and reflected the disease activity in multiple sclerosis. In this study, we sought to investigate whether MAIT cells are involved in the pathogenesis of systemic lupus erythematosus (SLE).

Methods:  Whole blood samples or peripheral blood mononuclear cells (PBMC) of SLE patients as well as healthy volunteers were stained with anti-human monoclonal antibodies(mAb) against CD3, γδTCR, Vα7.2TCR, CD161, CD45RA, CCR7, CD69, CD95(FAS) and 7-AAD. MAIT cells were identified as CD3⁺γδTCR^–Vα7.2TCR⁺CD161^highcells by FACS LSR Fortessa. In some experiments, costaining of intracellular active caspase-3 of MAIT cells was performed. MAIT cells and other T cell subsets were single-cell sorted by using FACS Aria II, and the usage of Vα7.2-Jα33 TCR of single-cell sorted cells was examined by PCR. PBMC labeled with Cell Trace Violet Dye were stimulated with anti-CD3mAb and anti-CD28mAb or IL-15, and the cell proliferation was analyzed by FACS. 

Results: As previously reported, the frequencies of γδT cells were slightly reduced in SLE. The percentages of MAIT cells from SLE patients were markedly decreased and about 7-fold lower compared with those from healthy subjects. Single-cell PCR analysis indicated that the decrease of lupus MAIT cells was not a result of downmodulation of surface markers. The proliferative capacity was slightly reduced in lupus MAIT cells. MAIT cells from lupus patients with active disease expressed high levels of CD69, and lupus MAIT cells had higher percentages of FAS^high cells, active caspase-3 or 7-AAD positive cells. These result suggest that more MAIT cells are undergoing activation-induced cell death in SLE.　Activated MAIT cells failed to expand in a long term culture. Although the frequencies of naïve cells were increased in lupus γδT cells, most MAIT cells displayed an effector memory phenotype and there was no increase of naïve cells among lupus MAIT cells. 

Conclusion: This study demonstrates that the frequency of MAIT cells was significantly reduced in SLE. The increased cell death and reduced cell prolifeation of activated MAIT cells were in part responsible for the decrease of MAIT cells in SLE. The limited recruitment of recent thymic emigrants of naïve MAIT cells also contributed the profound reduction of these cells in SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduction-of-mait-cell-frequency-associated-with-reduced-cell-proliferation-and-enhanced-cell-death-in-systemic-lupus-erythematosus/