CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40.
CD40 is a member of the tumor necrosis factor (TNF) receptor family of cell surface proteins and was originally described as a B cell restricted antigen. Treatment of primary human monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), or interferon gamma (IFN-gamma) resulted in the induction of CD40 mRNA and enhancement of cell surface protein expression. CD40 was found to mediate monocyte adhesion to cells expressing recombinant CD40 ligand. CD40 ligand-transfected cells provided a potent costimulus for monocyte TNF-alpha and IL-6 production in the presence of GM-CSF, IL-3, or IFN-gamma, and enhanced IL-8 production stimulated by GM-CSF or IL-3. In addition, CD40 ligand-transfected cells acting in the absence of a costimulus induced monocytes to become tumoricidal against a human melanoma cell target. Collectively, these data indicate that CD40 ligand is pleiotropic with potent biological activity on monocytes.
Alderson
M R
MR
Department of Cellular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
Armitage
R J
RJ
Tough
T W
TW
Strockbine
L
L
Fanslow
W C
WC
Spriggs
M K
MK
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics; D019013:CD40 Antigens; D023201:CD40 Ligand; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D007375:Interleukin-1 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D019013:CD40 Antigens; D016207:Cytokines; D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor