Increased cytotoxicity and CD16 (Leu 11) expression in long-term, IL-2-activated human peripheral blood mononuclear cells

Abstract

CD16 (Leu 11) positive cells are believed to be the effector cells for the so-called LAK phenomenon. Current evidence suggests that this cell population is comprised predominantly of IL-2-activated CD3 negative Leu 11+ NK cells and a minor proportion of Leu 11+ CD3+ MHC unrestricted type II cytotoxic T cells. The current study demonstrates a continuous increase in the frequency of Leu 11+ (and CD8+) cells and a decline of CD3 and CD4 positive cells during prolonged culture of human PMBL with high levels of rIL-2. Cytotoxicity also increases in this time period parallel with Leu 11 to a maximum of activity on the twelfth day of culture. This correlation suggests that the long-term activated killer cells generated in this period are Leu 11+, CD8+, CD3-, CD4- activated NK cells. With regard to tumor therapy, the long-term culture of PMBL in rIL-2 may be of advantage over short-term activation protocols. If the Leu 11+ cells are in fact the mediators of the therapeutic response, the long-term culture generates up to six times more effector cells. In addition, this method allows significant savings in the expense for leukophoresis, cell culture, and laboratory personnel. The efficacy of long-term, cultured rIL-2-activated Leu 11+ cells for tumor therapy is currently being investigated in clinical trails.