Neonatal deletion and selective expansion of mouse T cells by exposure to rabies virus nucleocapsid superantigen.
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.
Lafon
M
M
Unité de la Rage, CNRS UA 359, Institut Pasteur, Paris, France.
Scott-Algara
D
D
Marche
P N
PN
Cazenave
P A
PA
Jouvin-Marche
E
E
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*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens