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Spleen cells from B6C3F1hybrid mice pretreated i.v. with 5x107C3H spleen cells seven days earlier (C3H-pretreated B6C3F1) suppress the in vitro B6 anti-B6C3F1proliferative and cytotoxic responses, when they are added to cultures of B6 responding and B6C3F1stimulating spleen cells. This suppression is mediated by a Thy-1Lyt-12cell of C3H origin that is radiosensitive at 2000 rads. This suppressor cell is not induced by the injection to B6C3F1hybrids of spleen cells from the other parent strain (B6) or an allogeneic strain (D2). It does not suppress either the response of the other parent (C3H) or an allogeneic strain (D2) to B6C3F1antigens, or the response of B6 cells to an allogeneic strain (D2). Its induction depends upon the number and the subpopulation of C3H spleen cells injected since suppression is observed after the injection of more than 2.5X107C3H cells, and the suppression inducing cells have the phenotype Thy-1Lyt-12. This phenomenon is not limited to the C3H-B6C3F1genetic combination, since it has been observed in all parent hybrid combinations tested to date.

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.

B6D2F1hybrid mice pretreated i.v. with 5×107spleen cells from B6 donors seven days earlier (B6-pretreated B6D2F1hybrids) develop resistance to local GVHR induced by the subcutaneous injection of spleen cells of either B6 (GVHR-B6) or D2 (GVHR-D2) origin. This resistance has specific and a nonspecific components that concern the GVHR-B6 and the GVHR-D2, respectively. The two types of resistance to GVHR are neither induced under the same conditions nor mediated by the same mechanism.