EBAG9 tempers lymphocyte killing activity.

The cytotoxic activity of lymphocytes is crucial for immune surveillance and homeostasis. Several independent, naturally occurring genetic models characterized by defects in granule trafficking or exocytosis have helped to decipher the multiple steps and molecules that regulate the cytotoxic process. The study by Rüder and colleagues in this issue of the JCI shows that an engineered absence of EBAG9, previously reported as a tumor-associated antigen, enhances cytotoxic activity of CTLs but not NK cells, likely acting on the endosomal-lysosomal trafficking of the cytotoxic effectors (see the related article beginning on page 2184). This finding adds a new piece to the puzzle of complex mechanisms that tightly regulate the capacity of the cytotoxic response and suggests a new target to negatively modulate CTL responsiveness.