LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INDUCED IMMUNE DYSFUNCTION - INDUCTION OF AND RECOVERY FROM T-CELL ANERGY IN ACUTELY INFECTED MICE

Acute infection of immunocompetent mice by lymphocytic choriomeningiti s virus induces a potent cytotoxic T-lymphocyte response that eliminat es infectious virus. Concurrently and paradoxically, there is a genera l suppression of lymphocyte responses to mitogens and to other infecti ous agents. Splenocytes from infected mice released significant amount s of gamma interferon in response to mitogenic stimulation in vitro, b ut neither interleukin 2 nor interleukin 4 was similarly elevated rela tive to the amounts released by control cells. Early T-cell receptor-p roximal signaling events were found to be intact, confirming that the cells were viable and had received the mitogenic stimuli in an appropr iate manner. Acutely infected adult thymectomized mice regained concan avalin A responsiveness in parallel with euthymic mice, if T cells wer e left unmanipulated for several weeks after clearance of virus from t he mice. Therefore, although acute lymphocytic choriomeningitis virus infection has the effect of disrupting proliferation when the T-cell r eceptor is ligated, this state is only temporary. In contrast, T cells from persistently infected adult mice reveal long-lasting alterations in concanavalin A responsiveness.