The involvement of the cytoskeleton during antibody-dependent cellular cytotoxicity (ADCC)

The mechanism of initiation of antibody-dependent cellular cytotoxicity (ADCC) was analyzed using a model system consisting of sensitized chicken red blood cells (ChRBC) as targets and non-immunized Balb/c mouse splenocytes as effectors. Using a 51Cr release assay in parallel with electron and light microscopic observations, we were able to correlate the binding of target cells to effector cells with the subsequent lysis of the target cells. Untreated splenocytes are capable of binding and lysing a substantial number of target cells in the presence of anti-ChRBC. Splenocytes pretreated with the microfilament disrupting drug, cytochalasin D, display a significant reduction in their ability to bind and kill target cells. In contrast, splenocytes incubated with colchicine, a drug that disrupts microtubules, are slightly stimulated in both their binding and lysis of ChRBC. Our data suggest that microfilaments (but not necessarily microtubules) play an important role in the initial recognition and binding steps between effector and target cells which are prerequisite conditions for target killing in this ADCC system.