Session Type: Abstract Submissions (ACR)
Signaling lymphocytic activation molecule family member 4 (SLAMF4) engagement by its ligand SLAMF2 can mediate the cytotoxicity of CD8+ T cells and natural killer cells. SLE CD8+ T lymphocytes are reportedly defective in cytotoxicity. The aim of this study was to investigate the expression and function of SLAMF4 on SLE CD8+ T cells.
The expression of SLAMF4 and its adaptor SAP in healthy and SLE T cells were measured by Q-PCR, flow cytometry and western blot. T cells were treated by immobilized anti-SLAMF4 antibodies and the cytotoxic capacity of the T cells was monitored by the cell surface expression of CD107a, reflecting exocytosis of lytic granules.
We found significant downregulation of SLAMF4 and the adaptor molecule SAP gene and protein expression in SLE T cells compared to normal controls. Characterization of the T cell subsets revealed that SLE patients have significantly less SLAMF4+ CD8+ T cells compared to normal control T cells, switching the SLAMF4+/SLAMF4– ratio in the favor of SLAMF4– CD8+ T cells which have less SAP expression and decreased cytotoxic capacity. SLAMF4 engagement triggers the degranulation of CD8+ T cells and SLE T cells have decreased degranulation capacity compared to normal controls. In the effort to explain the loss of SLAMF4+ CD8+ T cells in SLE we found that these cells are more likely become double negative T cells and/or die by apoptosis.
Based on our results we conclude that the selective loss of SLAMF4+ CD8+ T cells may contribute to the ineffective capacity of fighting against infections in SLE.
G. C. Tsokos,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-selective-loss-of-slamf4-cd8-t-cells-contributes-to-the-decreased-cytotoxic-capacity-observed-in-systemic-lupus-erythematosus/