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Induction and Inhibition of CD40-CD40 Ligand Interactions: A New Strategy Underlying Host-Virus Relationships

Madhav D. Sharma^*, Maria Leite de Moraes, Flora Zavala, Christiane Pontoux^* and Martine Papiernik^1,*

^* Institut National de la Santé et de la Recherche Médicale (INSERM) U345, Institut Necker, and Centre National de la Recherche Scientifique, Unité de Recherche Associée 1461, and INSERM U25, Hôpital Necker, Paris, France

Interaction between CD40 and the CD40 ligand (CD40L) is required for mouse mammary tumor virus (MMTV) propagation. We found that Fas was expressed on B cells and CD40L on a small subset of viral superantigen-cognate T cells 12 h after MMTV(SW) infection. CD40L and Fas were down-regulated after 24 h. All CD4 T cells then became resistant to anti-CD3-induced CD40L induction in vitro for 2 wk. Initiation of CD40L expression and its rapid shut-off was associated with IL-12 production and was controlled by IFN- and shedding of soluble CD40. These results suggest that a rapid, transient CD40-CD40L interaction involving a small number of cells is sufficient for MMTV propagation. Modulation of CD40L expression may be a major mechanism regulating the balance between viral propagation and host defenses, allowing mutual survival.

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