T‐Cell Effector Function and Unresponsiveness in the Murine Lymphocytic Choriomeningitis Virus Infection

When the virus dose is increased from 10 2 (low dose) to 10 4 LD 50 (high dose) a fatal lymphocytic choriomeningitis virus (LCMV) infection is changed into a subclinical one, and a selective virus‐specific delayed‐type hypersensitivity (DTH) unresponsiveness is induced, while the cytotoxic T‐cell response remains essentially unchanged. When low‐dose spleen effectors were transferred intravenously into intracerebrally infected high‐dose mice, fatal LCM disease occurred, which means that infected central nervous system target structures in these animals are sensitive to virus‐specific T cells. When low‐dose cells were transferred to intravenously infected high‐dose mice, these animals regained their T D function (the effect of T cells mediating DTH). Since this indicates that the survival of intracerebrally infected high‐dose mice is intimately linked with the absence of virus‐specific DTH reactivity, a search for T suppressor (T s ) activity in these animals was performed by transferring high‐dose spleen cells to lethally (intracerebrally) infected low‐dose recipients. In this way we obtained an afferent suppression, which was not H‐2 restricted, but was abrogated when the spleen cells were pretreated with neutralizing anti‐LCMV serum, indicating a suppressive effect of virus transferred with the infected cells. When tolerance induction was attempted with virus alone, a potentially fatal immune reaction could be altered to unresponsiveness (i.e. survival) as late as 4 days after an otherwise lethal infection with LCMV. The results indicate that the maturation of the virus‐specific T D response is sensitive to large amounts of virus antigen. We conclude that this impairment and the resulting DTH unresponsiveness is due to a clonal deletion or anergy rather than to the effect of T s cells, and that the T D effector function is critical to the development of fatal LCM disease.