The antibody-independent cytotoxic activity of normal circulating human leucocytes. I. Lysis of target cells by monocytes and neutrophils in a non-phagocytic pathway.

Normally circulating human leucocytes were found to consistently lyse rabbit erythrocyte (RRBC) target cells within 24 hr in culture. The reaction is referred to as the naturally-occurring cell-mediated cytotoxic, or NOCC, reaction. Characteristics of this cytotoxic reaction are as follows. (i) The cytotoxic reaction described here can be distinguished from the antibody-dependent cellular cytotoxic (ADCC) reaction as conventional Fc receptors do not appear to play a role. Although the cytotoxic reaction occurs optimally in medium fortified with normal human serum to a final concentration of 1%, neither antibodies nor immunoglobulins in general appear to play a role. Agamma human serum or purified human serum albumin without detectable immunoglobulins are as capable of facilitating and sustaining the NOCC cytotoxic reaction as is normal human serum. Furthermore, foetal calf serum, which promotes the ADCC cytotoxic reaction, inhibits the NOCC cytotoxic reaction. (ii) The NOCC reaction is not a phagocytic one as phagocytosis of the RRBC could not be detected during the culture period. (iii) Monocytes and neutrophils, but not lymphocytes, are capable of lysing the target cells in the NOCC reaction. The effector mononuclear cell is a monocyte with receptors for Fc and C'3. (iv) The NOCC cytotoxic reaction is dependent upon direct effector cell--target cell contact and not upon soluble mediators secreted by the effector cells since third-party bystander erythrocytes are not lysed in the presence of rabbit erythrocyte target cells and human mononuclear cells. Supernatants from lysed RRBC target cells could not lyse fresh RRBC. It is concluded that the NOCC cytotoxic reaction utilizing rabbit erythrocytes as target cells permits the identification of cytotoxic subclasses of monocytes and neutrophils.