Target selectivity of interferon-induced human killer lymphocytes related to their Fc receptor expression.

Abstract

Human blood lymphocytes were fractionated on the basis of surface characteristics such as adherence to nylon wool and expression of erythrocyte (E) and Fc receptors. The various subsets were incubated with interferon for 3 hr. Two cell lines that differ in sensitivity to the natural killer effect, K562 and Daudi, were exposed to these lymphocytes (i.e., their sensitivity to interferon-activated killing was tested). Cell line Daudi, with a low sensitivity to the natural killer effect, was also affected by interferon-activated killing. The efficiency of the nonadherent subsets, separated accor in to the expression of E receptor, ranked similarly in natural killing (anti-K562) and interferon-activated killing (anti-K562 and anti-Daudi) in the following order: E receptor-negative cells, low-affinity E receptor-positive cells, and high-affinity E receptor-positive cells.Further separation on the basis of Fc receptor expression revealed a difference between the two targets. The Fc receptorpositive and -negative cells that did not express high-affinity E receptors killed K562 with similar efficiency whereas Daudi cells were more sensitive to the effect of cells devoid of Fc receptor. Results obtained with other targets suggested that T cell lines behave similarly to K562 and that the difference may be generally valid for T and B cell lines.

Natural and activated cytotoxic lymphocytes which act on autologous and allogeneic tumor cells

“…It is significant that IAK was found to be mediated by the same lymphocyte subsets as NK [14,23]. The rank order of the lymphocyte subsets was similar, but the IAK effects were stronger.…”

“…Cells with high-avidity E receptors without Fc receptors. The importance of the T cells in the NK function was als0 indicated by the preferential sensitivity of Daudi cells to the subsets, which have since been shown to contain cells reacting with the T monoclonals [14].…”

“…They are heterogeneous with regard to their surface marker characteristics. The anti-K562 rank order of different nylon-nonadherent subfractions obtained after separation on the basis of SRBC rosetting and FcR expression is as follows [14]; 1. Non-SRBC-rosetting subset with and without demonstrable Fc receptors.…”

Lymphocyte-mediated lysis of tumor cells in vitro antigen-restricted clonal and unrestricted polyclonal effects

“…This is reflected in the dose-response curves when a constant number of target cells are exposed to a different number of effector cells. If the lymphocytes are exposed to various in vitro manipulations such as interferon (IFN) treatment or addition of phytohemagglutinin (PHA) during the assay, their activity increases [4,43,46]. With exceptionally high NK-active donors, neither of these two enhancing treatments was found to substantially increase the lytic effect.…”

“…This suggests that the lytic potential required for the killing of the particular target cell was already maximal [-46]. IFN-induced potentiation of cytotoxicity, IFNactivated killing (IAK), occurs in those lymphocyte subsets which also exert the function spontaneously [46,60]. Therefore, the distinction between NK and IAK may be only operational.…”