Increased SLAMF7+CD8+ T cells are associated with the pathogenesis of experimental autoimmune pancreatitis in mice

Abstract

Background: IgG4-related autoimmune pancreatitis (AIP) is considered to be a T cell-mediated autoimmune disease. However, CD8⁺ T cells have only received brief mention, and have yet to be completely studied. The study aimed to investigate the expression of signaling lymphocytic activation molecule family 7 (SLAMF7) on CD8⁺ T cells and the features of SLAMF7⁺CD8⁺ T cells in MRL/Mp mice with AIP.

Methods: A murine model of AIP was established by intraperitoneal injection with polyinosinic:polycytidylic acid (poly I:C) for 8 weeks. Dexamethasone treatment was daily administrated for the last 2 weeks during a 6-week course of poly I:C. SLAMF7 expression on CD8⁺ T cells in the spleen and pancreas was detected by flow cytometry. Granzyme B (GZMB) and cytokines including IFN-γ, TNF-α, and IL-2, were monitored in an in vitro T cell activation assay. Dexamethasone suppression assays were performed to downregulate SLAMF7 expression on T cells upon T cell receptor stimulation.

Results: AIP in MRL/Mp mice was induced by repeated intraperitoneal administration of poly I:C and CD8⁺ T cells were increased in the inflamed pancreas. SLAMF7⁺CD8⁺ T cells were elevated in the spleen and pancreas of AIP mice. SLAMF7⁺CD8⁺ T subsets produced more GZMB, IFN-γ, TNF-α and IL-2 than SLAMF7^-CD8⁺ T subsets. Dexamethasone treatment ameliorated pancreatic inflammatory and fibrosis of AIP. Dexamethasone could downregulate SLAMF7⁺CD8⁺ T cells and reduce GZMB, IFN-γ and TNF-α levels both in vitro and in vivo.

Conclusions: Increased SLAMF7⁺CD8⁺ T cells exhibit enhanced cytotoxicity and cytokines secretion capacity, which may be involved in the pathogenesis of AIP.

Keywords: Autoimmune pancreatitis; CD8(+) T cells; Dexamethasone; SLAMF7.