Accessory signaling by CD40 for T cell activation: induction of Th1 and Th2 cytokines and synergy with interleukin-12 for interferon-gamma production.
The interaction of CD40 ligand (CD40L) on activated T cells with CD40 on B cells, monocytes and dendritic cells is essential for humoral immunity and for up-regulation of antigen-presenting cell (APC) functions, as a result of signaling through CD40. There are also some indications that after interaction with CD40, CD40L can directly signal T cells. In this study we demonstrate that upon stimulation of human peripheral blood T cells through the T cell receptor (TCR)/CD3 complex, CD40/CD40L interaction strongly enhances the production of Th1 cytokines such as interleukin (IL)-2 and interferon (IFN)-gamma and Th2 cytokines such as IL-4, IL-5 and IL-10 by a direct effect on T cells. Furthermore, CD40/CD40L interaction synergizes with IL-12 in selectively enhancing IFN-gamma production by purified anti-CD3-stimulated T cells. These effects were observed at both the protein and the mRNA level. Both CD4+ and CD8+ T cells were able to produce IFN-gamma in the presence of helper signals from IL-12 and CD40, although CD8+ T cells were less active. Since CD40/CD40L interaction also up-regulates IL-12 production and B7 expression by APC, our results suggest that CD40/CD40L interaction is bidirectional, and promotes activation of both APC and T cells.
Peng
X
X
Department of Pathophysiology, Catholic University of Leuven, Belgium.
Kasran
A
A
Warmerdam
P A
PA
de Boer
M
M
Ceuppens
J L
JL
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D019013:CD40 Antigens / Q000494:pharmacology*; D023201:CD40 Ligand; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology*; D008024:Ligands; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
D019013:CD40 Antigens; D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma