Session Title: T-cell Biology and Targets in Autoimmune Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: Mucosal-associated invariant T (MAIT) cells are a subset of innate-like lymphocytes which are restricted by the MHC-related molecule-1 (MR1) and express an invariant TCRα chain:Vα7.2-Jα33 in humans and Vα19-Jα33 in mice with a limited set of Vβ chains. Although the function of MAIT cells is not well known, like other innate-like lymphocytes, MAIT cells have been suggested to play both proinflammatory and regulatory roles in autoimmune models. We previously demonstrated that MAIT cells exerted a suppressive activity on T cells and the frequency of MAIT cells was reduced in patients with multiple sclerosis. In this study, we sought to investigate mechanisms by which MAIT cells are activated/inactivated and whether MAIT cells are relevant to other human autoimmune diseases including 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, invariant Vα7.2TCR, and CD161 and analyzed by FACS. MAIT cells were identified as CD3+γδTCR–Vα7.2TCR+CD161highcells. PBMC or FACS sorted MAIT cells were labeled with CellTrace Violet dye and stimulated with anti-CD3mAb and anti-CD28mAb or various types of cytokines. 6-7 days later, the cell proliferation was analyzed by FACS.
Results: As previously demonstrated, the frequency of MAIT cells of healthy controls was about 5% among T cells. The percentages of MAIT cells of SLE patients were 10-fold lower compared with those of healthy subjects. MAIT cells proliferated upon TCR stimulation when cultured with other PBMC. However, sorted MAIT cells failed to respond to anti-CD3mAb and anti-CD28mAb stimulation. MAIT cells and γδT cells were activated and proliferated by IL-15 even without exogenous TCR stimuli. MAIT cell proliferation was markedly suppressed by IFNα, but IFNα had little effect on TCR-stimulated γδT cell proliferation.
Conclusion: This study demonstrates that MAIT cell activation greatly depends on cytokines. As IFNα is known to be related to the pathogenesis of SLE, the abnormal balance of cytokines may be responsible to the reduced frequency of MAIT cells in SLE.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mucosal-associated-invariant-t-cells-are-inactivated-by-ifn%ce%b1-and-reduced-in-systemic-lupus-erythematosus/