Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Mucosal Associated Invariant T (MAIT) cells express a semi invariant T-cell receptor (TCR) (TCRVα7.2) restricted to MHC related protein 1 (MR1) and are able to be activated by a TCR-independent pathway involving IL-12 and IL-18. As these cytokines are involved in the pathogenesis of Giant Cell Arteritis (GCA), we investigated the role of MAIT cells in GCA.
Methods: Blood samples from 27 GCA patients, as defined by ≥3/5 ACR criteria, were obtained at diagnosis before starting glucocorticoid (GC) and compared with 16 healthy subjects (age >50 years, CRP≤5 mg/L with no infectious, auto-immune or neoplastic disease). A second blood sample was obtained after 3 months of treatment for 20/27 GCA patients. MAIT cells (CD3+CD4–TCRγd–TCRVα7.2+CD161+) were quantified and their phenotype analyzed by flow cytometry. For 4 patients and 5 controls, MAIT cells and MAIT depleted CD161+ T cells were sorted using Fluorescent Assisted Cell sorting (FACS), stained with cell trace violet (invitrogen) and cultured with or without anti CD3/CD28 microbeads or IL-12 and IL-18 (50 ng/ml each). Proliferation index was assessed by flow cytometry after 7 days of culture. MAIT (CD3+TCRVα7.2+IL-18R+) were stained in positive and negative Temporal Artery Biopsies (TAB) by confocal microscopy on a Leica TCS SP8 confocal microscope. Results are expressed as median [interquartile range] and P value is the result of Mann Whitney or Wilcoxon ranked tests, as appropriate.
Results: MAIT frequency among circulating αβ-T cells was similar between patients at diagnosis and controls (0.48% [0.15-1.01] vs. 0.47% [0.28-1.13]; P=0.63) and not modified after GC-treatment (0.48% [0.15-0.76] vs. 0.43% [0.14-0.88]; P=0.51). By contrast, the phenotype of MAIT cells was modified toward a decreased expression in CXCR3 (6.08% [1.57-13.96] vs. 8.33% [6.13-36.66]; P=0.048) and an increased expression in IFN-γ (47.7% [31.8-66.7] vs. 31.0% [16.6-38.7]; P=0.03) in patients when compared to controls. This difference was not corrected after GC-treatment: from 8.31% [3.90-16.30] to 4.36% [16.40-17.47] (P=0.96) for CXCR3 expression and from 39.8% [23.7-61.3] to 42.4% [23.5-63.3] (P=0.85) for IFN-γ expression. Functional analyses revealed that MAIT proliferate in the presence of IL-12 and IL-18 without TCR activation, unlike MAIT-depleted CD161+ T cells. Notably, MAIT from GCA patients displayed a stronger proliferation than the one from controls when stimulated with IL-12 and IL-18: proliferation index 3.39 [2.36-7.15] vs. 1.40 [1.20-2.42] (P=0.03). MAIT cells (CD3+IL-18R+TCRVα7.2+ cells) were identified in the arterial wall of 3 positive TABs and absent in 3 negative TAB.
Conclusion: Although MAIT frequency is not modified in the blood of GCA patients, MAIT infiltrate the arterial wall in GCA patient and their functional characteristics are modified toward a pro-inflammatory phenotype: increased IFN-γ expression and stronger proliferation ability in presence of IL-12 and IL-18. As IL-12 and IL-18 are produced by dendritic cells and macrophages in GCA lesions, MAIT cells might be activated by a TCR-independent pathway and play a role in GCA pathogenesis through the production of IFN-γ.
To cite this abstract in AMA style:Ghesquière T, Ciudad M, Greigert H, Gerard C, Cladière C, Thebaut M, Guilhem A, Leguy-Seguin V, Berthier S, Falvo N, Nicolas B, Maillet T, devilliers h, Bielefeld P, Vernier N, Maurier F, Ornetti P, Quipourt V, Gabrielle P, Creuzot-Garcher C, Martin L, Audia S, Bonnotte B, Samson M. Mucosal Associated Invariant T Cells in Giant Cell Arteritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/mucosal-associated-invariant-t-cells-in-giant-cell-arteritis/. Accessed April 13, 2021.
« Back to 2019 ACR/ARP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/mucosal-associated-invariant-t-cells-in-giant-cell-arteritis/