Figure 1.

Schematic overview of antigen specific CD8+ T-cell response in a normal individual (A) and in a patient with hemophagocytic syndrome (B). In response to an infectious trigger, antigen-specific CD8⁺ T cells transiently undergo massive expansion, use cell-mediated cytolysis, and produce interferon-γ (IFN-γ). After pathogen clearance, this immune response is self-limiting and most cells die, leaving a reduced number of memory T and B cells. During the course of hemophagocytic syndrome, uncontrolled expansion of antigen-specific effectors occurs. Activated lymphocytes secrete high levels of INF-γ and induce a feedback loop on macrophage and T cells, which continuously activate each other and expand. High levels of inflammatory cytokines are secreted, including IFNγ, tumour necrosis factor-α, interleukin (IL)-1, IL-6, and IL-18. Activated macrophages phagocytose bystander hematopoietic cells (hemophagocytosis). Activated lymphocytes and macrophages infiltrate various organs, resulting in massive tissue necrosis and organ failure.