INTERLEUKIN-12-ACTIVATED NATURAL-KILLER-CELLS RECOGNIZE B7 COSTIMULATORY MOLECULES ON TUMOR-CELLS AND AUTOLOGOUS DENDRITIC CELLS

Activation of natural killer (NK) cells in the presence of interleukin -12 (IL-12) augments the capacity of these effector cells to recognize B7-1- and B7-2-expressing target cells. These effector cells also eff iciently lyse autologous B7-positive progenitor or organ-derived dendr itic cells, suggesting a physiologic regulatory pathway between IL-12, NK cells, and B7-expressing antigen-presenting cells, Although IL-12- activated NK cells secreted higher levels of interferon-gamma, this cy tokine did not play a role in synergistic effects of IL-12 and B7 on N K activation, The B7-counterreceptor was found to be selectively upreg ulated on IL-2/IL-12 as compared with IL-2-activated NK cells, CD28 is functionally involved in the recognition of B7 an target cells since IL-2/IL-12-activated NK cells derived from CD28 knockout mice were str ongly reduced in their capacity to lyse syngeneic B7-positive tumor ce lls as well as antigen-presenting cells. However, recognition of B7 on allogeneic targets did not require the expression of CD28 on the IL-2 /IL-12-activated NK cells, Hence, IL-12 triggers the expression of bot h CD28-dependent and CD28-independent mechanisms that allow NK cells t o eliminate B7-positive target cells including autologous dendritic ce lls. (C) 1998 by The American Society of Hematology.