Nonspecific cytotoxic cells as effectors of immunity in fish

Abstract

Nonspecific cytotoxic cells (NCC) may be the teleost fish equivalent of mammalian natural killer (NK) cells. Although significant differences exist between species regarding many characteristics of these cells, both NCC and NK cells share similarities: in the types of target cells sensitive to lysis; in mechanisms of target cell recognition; in the requirements for a competent lytic cycle; and both types of effectors participate in mediating the lysis of infectious microorganisms. A putative antigen binding receptor obtained from catfish NCC has now been characterized using monoclonal antibodies (mabs). This receptor is a vimentin-like protein. Preliminary studies indicate that NCC recognize a 40 kD protein on the membranes of susceptible target cells. Solubilized target cell protein can specifically bind to NCC and inhibit killing.Similar to NK cells, NCC require cell contact with the target cell to deliver the lethal cytotoxic hit. NCC appear to be the more potent cytotoxic cells because fewer are required to kill an individual target cell and less time is required for this action to occur than for NK cells. Unlike NK cells, NCC do not recycle under experimental conditions. Preliminary studies were also reviewed to characterize signal transduction responses. Monoclonal antibody against the vimentin-like protein receptor activates NCC cytotoxicity, initiates the production of significant increased levels of free cytoplasmic calcium, and causes the production of inositol lipid intermediates (specifically phosphotidylinositol 1, 4–5 trisphosphate). NCC may be important effectors of anti-parasite immunity. Although these cells probably do not elicit memory responses, data suggest that they do recognize antigen and can be activated and recruited into peripheral tissue where they mediate cytolytic responses.