Shark spontaneous cytotoxicity: characterization of the regulatory cell

Down regulation of shark macrophage-mediated spontaneous cytotoxicity is evident in vitro when animals are maintained at environmental temperatures greater than 26 degrees C. Previous work has shown that inhibition of spontaneous killing is mediated by viable, glass nonadherent, nonphagocytic cells which are sensitive to alterations in environmental temperature. The current report further characterizes the regulatory cell population. Glass nonadherent leukocytes were enriched for regulatory activity by density gradient centrifugation, and the majority of activity sedimented to 34% iso-osmotic Percoll. Two morphologically distinct cells are found in this fraction, lymphocyte-like cells and granulocytes. The 34% fraction was further separated by adherence to SIg-coated dishes, and the ability to inhibit spontaneous killing partitioned with the SIg- subset. In addition, fractionation of cells bearing Fc receptors (FcR) for shark Ig showed the regulator to be devoid of FcR. Sequential depletion of cells expressing SIg and FcR confirmed these data. Inhibition by allogeneic cells indicated that histocompatibility between the cytotoxic effector and the regulator is not a requirement for expression of activity. Thus, down regulation of spontaneous cytotoxicity is mediated by nonadherent, nonphagocytic, SIg-, FcR-cells which are not MHC restricted. The lymphoid or granulocytic lineage of the regulatory cell is discussed.