INDUCTION AND INHIBITION OF CD40-CD40 LIGAND INTERACTIONS - A NEW STRATEGY UNDERLYING HOST-VIRUS RELATIONSHIPS

Interaction between CD40 and the CD40 ligand (CD40L) is required for m ouse mammary tumor virus (MMTV) propagation. We found that Fas was exp ressed on B cells and CD40L on a small subset of viral superantigen-co gnate T cells 12 h after MMTV(SW) infection. CD40L and Fas were down-r egulated after 24 h, All CD4 T cells then became resistant to anti-CD3 -induced CD40L induction in vitro for 2 wk. Initiation of CD40L expres sion and its rapid shut-off was associated with IL-12 production and w as controlled by lFN-gamma and shedding of soluble CD40, These results suggest that a rapid, transient CD40-CD40L interaction involving a sm all number of cells is sufficient for MMTV propagation. Modulation of CD40L expression may be a major mechanism regulating the balance betwe en viral propagation and host defenses, allowing mutual survival.