THE ANTIBODY-INDEPENDENT CYTO-TOXIC ACTIVITY OF NORMAL CIRCULATING HUMAN-LEUKOCYTES .1. LYSIS OF TARGET-CELLS BY MONOCYTES AND NEUTROPHILS IN A NONPHAGOCYTIC PATHWAY

  • 1 January 1981
    • journal article
    • research article
    • Vol. 44  (1) , 97-107
Abstract
Normally circulating human leukocytes consistently lysed rabbit erythrocyte (RRBC) target cells within 24 h in culture. The reaction is referred to as the naturally-occurring cell-mediated cytotoxic (NOCC) reaction. Characteristics of this cytotoxic reaction are described. This cytotoxic reaction 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 Ig in general appear to play a role. Agamma human serum or purified human serum albumin without detectable Ig are as capable of facilitating and sustaining the NOCC cytotoxic reaction as is normal human serum. Fetal calf serum, which promotes the ADCC cytotoxic reaction, inhibits the NOCC cytotoxic reaction. The NOCC reaction is not a phagocytic one as phagocytosis of the RRBC was not detected during the culture period. 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 [complement] C3. The NOCC cytotoxic reaction is dependent upon direct effector cell-target cell contact and not upon soluble mediators secreted by the effector cells since 3rd-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. The NOCC cytotoxic reaction utilizing rabbit erythrocytes as target cells evidently permits the identification of cytotoxic subclasses of monocytes and neutrophils.