IL-12 up-regulates CD40 ligand (CD154) expression on human T cells.
IL-12 is a heterodimeric cytokine produced by APC that promotes the development of CD4+ Th1 cells and their IFN-gamma production after TCR/CD3 triggering. We here investigated the capacity of IL-12 to modify the expression on T cells of CD40 ligand (CD40L or CD154), a molecule transiently expressed on activated T cells and known to be of utmost importance for cognate interaction with B cells and for activation of dendritic cells and macrophages. Our data demonstrate that IL-12 up-regulates CD40L expression on anti-CD3-activated human peripheral blood T cells. For optimal induction of CD40L, IL-12 synergizes with IL-2 as well as with other costimulatory interactions, such as B7/CD28. The effect of IL-12 was observed at both the protein and the mRNA level. T cells costimulated by IL-12 provided more efficient help for IL-4-dependent B cell proliferation and for IgG production than when activated in the absence of IL-12. This helper activity was blocked by an mAb against CD40L, indicating that the effect of IL-12 on B cells is mediated indirectly through CD40L. The data thus suggest that the effects of IL-12 on cellular and humoral immune responses are partly mediated through CD40L induction.
Peng
X
X
Department of Pathophysiology, Faculty of Medicine, Catholic University of Leuven, Belgium.
Remacle
J E
JE
Kasran
A
A
Huylebroeck
D
D
Ceuppens
J L
JL
D016475:3T3 Cells; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000494:pharmacology; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D008024:Ligands; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D019013:CD40 Antigens; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D012333:RNA, Messenger; D023201:CD40 Ligand; D018664:Interleukin-12