title: Direct physical interaction involving CD40 ligand on T cells and CD40 on B cells is required to propagate MMTV.
abstract: The propagation of mouse mammary tumor virus (MMTV) has been analyzed in mice defective for expression of CD40 ligand (CD40L). Mice with endogenous viral superantigen (SAG) delete T cells with cognate V beta independent of CD40L expression. Nevertheless, CD40L-mice do not show deletion of cognate T cells after being exposed to infectious MMTV and have greatly diminished viral replication. The response of CD40L- T cells to SAG in vitro is also impaired, but can be reconstituted by adding B cells activated by recombinant CD40L to express costimulatory molecules. Thus, direct CD40L-dependent B cell activation appears to be a critical step in the life cycle of MMTV. The initial step in SAG-dependent T cell activation, and hence the MMTV life cycle, may be mediated by non-B cells, because splenocytes from B cell-deficient SAG-transgenic mice are able to activate cognate T cells.
authors.affiliation: Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, Connecticut 06510, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Chervonsky
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: A K
authors.initials: AK
authors.lastname: Barlow
authors.forename: M
authors.initials: M
authors.lastname: Khery
authors.forename: R A
authors.initials: RA
authors.lastname: Flavell
authors.forename: C A
authors.initials: CA
authors.lastname: Janeway
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology / Q000821:virology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D002450:Cell Communication; D008213:Lymphocyte Activation; D008324:Mammary Tumor Virus, Mouse / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000502:physiology / Q000821:virology*; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand