CD8⁺ T cells from CLL patients show defective cytotoxicity because of failure of granzyme localization to the immunologic synapse. The cytotoxic activity of CD8⁺ T cells from CLL patients was assessed further. (A) CD8⁺ T cells from CLL patients retain the ability to degranulate in response to SEB, as shown by their increased ability to transfer CD107a to the cell surface. (B) Healthy CD8⁺ T cells showed effective F-actin (red, rhodamine phalloidin) immunologic synapse formation with colocalization of CD107a (yellow, Alexa Fluor 647) and granzyme B (green, Alexa Fluor 488) at the synapse contact site with healthy B cells (+sAg). (C) In contrast, CD8⁺ T cells from CLL patients fail to form effective F-actin immune synapses with autologous CLL cells (+sAg) that is associated with strong, nonpolarized expression of CD107a and a lack of granzyme B polarization to the contact site.