title: Neonatal deletion and selective expansion of mouse T cells by exposure to rabies virus nucleocapsid superantigen.
abstract: The nucleocapsid (NC) of the rabies virus behaves as an exogenous superantigen (SAg) in humans. In the present report, we analyzed whether it is also a SAg in mice by studying the effect of NC on T cell receptor (TCR) V beta expression in BALB/c mice. Repeated injection of NC in newborn BALB/c mice led to a marked reduction by two- to sixfold of V beta 6 expressing CD4+ T cells in spleen and in peripheral blood. Decrease of V beta 6-expressing CD3+ mature T cells was also observed in thymus. Single NC injection in footpad resulted in a three- to sixfold expansion of V beta 6 CD4+ T cells, but not of CD8+ T cells, in the draining lymph nodes of BALB/c mice. The intensity of the stimulation was dose dependent and was maximal 3 d after the NC injection. The clonal deletion of T cells bearing a particular V beta demonstrates that NC is a SAg in mice. T cells, especially CD4+ T cells, are an essential factor in host resistance to rabies virus and also in the pathophysiology of paralysis; thus, we postulate that a rabies virus component, which stimulates T cells, such as a SAg, may increase virus immunopathogenicity. To evaluate this hypothesis, we compared the course of rabies in adult BALB/c lacking V beta 6, 7, 8.1, and 9 T cells and in normal BALB/c. Immune-related paralysis was decreased in BALB/c missing the NC target V beta T cells. Transfer of V beta 6 but not of V beta 8.1-3 T cells into recipient mice lacking V beta 6, 7, 8.1, and 9 allowed the immune-related paralysis to evolve. Taken together, these results strongly support the hypothesis that T cells expressing rabies SAg-specific V beta 6 T cells, are involved in the genesis of the immunopathology that is characteristic of paralytic rabies.
authors.affiliation: Unité de la Rage, CNRS UA 359, Institut Pasteur, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Lafon
authors.forename: D
authors.initials: D
authors.lastname: Scott-Algara
authors.forename: P N
authors.initials: PN
authors.lastname: Marche
authors.forename: P A
authors.initials: PA
authors.lastname: Cazenave
authors.forename: E
authors.initials: E
authors.lastname: Jouvin-Marche
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002213:Capsid / Q000276:immunology*; D017637:Clonal Deletion; D006224:Cricetinae; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011820:Rabies virus / Q000276:immunology*; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000502:physiology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens