ACCESSORY SIGNALING BY CD40 FOR T-CELL ACTIVATION - INDUCTION OF TH1 AND TH2 CYTOKINES AND SYNERGY WITH INTERLEUKIN-12 FOR INTERFERON-GAMMAPRODUCTION

The interaction of CD40 ligand (CD40L) on activated T cells with CD40 on B cells, monocytes and dendritic cells is essential for humoral imm unity and for up-regulation of antigen-presenting cell (APC) functions , as a result of signaling through CD40. There are also some indicatio ns that after interaction with CD40, CD40L can directly signal T cells . In this study we demonstrate that upon stimulation of human peripher al blood T cells through the T cell receptor (TCR)/CD3 complex, CD40/C D40L interaction strongly enhances the production of Th1 cytokines suc h as interleukin (IL)-2 and interferon (IFN)-gamma and Th2 cytokines s uch 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 enhancin g 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 le ss active. Since CD40/CD40L interaction also upregulates IL-12 product ion and B7 expression by APC, our results suggest that CD40/CD40L inte raction is bidirectional, and promotes activation of both APC and T ce lls.