Cytotoxic T cell (CD8⁺)

Because almost every nucleated cell expresses MHC class I and continually displays fragments of its own cytosolic proteins on it, CD8 T cells can detect infection or malignancy in any tissue. A naive CD8 T cell is primed in a lymph node by a dendritic cell — either one infected by the virus or one that has cross-presented antigen from an engulfed infected cell — usually with CD4 help, which "licenses" the DC through CD40L–CD40 and supplies IL-2. It then proliferates and differentiates into an effector cytotoxic T lymphocyte (CTL) loaded with cytotoxic granules and migrates to the infected tissue.

When a CTL's TCR engages the right peptide–MHC I complex on a target, it forms a tight immunological synapse and secretes the contents of its granules directly onto the target: perforin polymerises to form pores in the target membrane, allowing granzymes (serine proteases) to enter and activate caspases, triggering apoptosis. CTLs also kill through Fas ligand binding Fas (CD95) on the target, and secrete IFN-γ and TNF-α, which inhibit viral replication and upregulate MHC expression. Apoptosis dismantles the target cell from within, destroying viral replication machinery without spilling virus or causing inflammation. Each CTL detaches unharmed and can kill many targets in succession (serial killing).