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 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-gamma, 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.
Geldhof
A B
AB
Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel (VUB), Brussels,
Moser
M
M
Lespagnard
L
L
Thielemans
K
K
De Baetselier
P
P
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000473:pathology; D051379:Mice; D008806:Mice, Inbred AKR; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D014411:Neoplastic Stem Cells / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D018106:CD28 Antigens; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma