IL-15/NKG2D signaling-mediated activation of CD8

Background: Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, accompanied by immune dysregulation, leading to a high mortality rate. Memory CD8 Methods: A mouse sepsis model was set up using cecum ligation and puncture (CLP), and the progression of sepsis was observed through IL-15 intervention. Serum inflammatory factors and organ damage markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine (CREA)] were detected by ELISA and biochemical analysis. HE staining was employed to assess pathological alterations in the spleen and multiple organ tissues. Immunohistochemical analysis was performed to detect CD8 expression in the liver, lung, kidney, and spleen. Flow cytometry was used to analyze the expression of NKG2D, initiation markers (CD38/HLA-DR), and effector molecules [Granzyme B, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α)] in splenic CD44 Results: Exogenous IL-15 significantly aggravated multi-organ damage (elevated AST, ALT, LDH, BUN, and CREA) and systemic inflammatory response in septic mice. Histopathological examination revealed splenic lymphocyte necrosis and worsening liver and kidney damage. Exogenous administration of IL-15 significantly enhances the recruitment and infiltration of CD8 Conclusions: IL-15 activates a TCR-independent bypass activation pathway by inducing NKG2D expression on memory CD8