Granzyme K-expressing CD8(+) T cells, complement activation and histotoxic immunity.

Granzyme K–expressing CD8+ T cells activate the complement cascade rather than directly executing apoptosis, defining a distinct lymphocyte-driven complement activation pathway.

• Why it matters: Most CD8+ T cell granzymes, like granzyme B, kill by intracellular substrate cleavage, leaving how GZMK shapes tissue inflammation and chronic disease unclear.
• What they did: This Perspective summarizes recent evidence that CD8+ T cells producing GZMK trigger complement activation and have distinct pro-inflammatory effects in tissues, including a proposed heritable trait in memory subsets.
• The result: The work frames “tissue histotoxicity” as a defense strategy acting on a tissue neighborhood rather than one cell at a time, linked to chronic and inflammatory diseases.

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