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 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-gamma 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.
Sharma
M D
MD
Institut National de la Santé et de la Recherche Médicale U345, Institut Necker, Paris, France.
Leite de Moraes
M
M
Zavala
F
F
Pontoux
C
C
Papiernik
M
M
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000502:physiology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008024:Ligands; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012192:Retroviridae Infections / Q000097:blood / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000821:virology; D014412:Tumor Virus Infections / Q000097:blood / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D019013:CD40 Antigens; D007106:Immune Sera; D008024:Ligands; C084778:M12 protein, Mouse mammary tumor virus; D008562:Membrane Glycoproteins; D018089:Superantigens; D014759:Viral Envelope Proteins; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma