Interleukin-12–Activated Natural Killer Cells Recognize B7 Costimulatory Molecules on Tumor Cells and Autologous Dendritic Cells

• Published in: Blood Vol. 91; no. 1; pp. 196 - 206
• Main Authors: Geldhof, Anja B., Moser, Muriel, Lespagnard, Laurence, Thielemans, Kris, De Baetselier, Patrick
• Format: Journal Article
• Language: English
• Published: 01.01.1998
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V91.1.196.196_196_206

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 efficiently lyse autologous B7-positive progenitor or organ-derived dendritic 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-γ, this cytokine did not play a role in synergistic effects of IL-12 and B7 on NK activation. The B7-counterreceptor was found to be selectively upregulated on IL-2/IL-12 as compared with IL-2–activated NK cells. CD28 is functionally involved in the recognition of B7 on target cells since IL-2/IL-12–activated NK cells derived from CD28 knockout mice were strongly reduced in their capacity to lyse syngeneic B7-positive tumor cells 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 both CD28-dependent and CD28-independent mechanisms that allow NK cells to eliminate B7-positive target cells including autologous dendritic cells.