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

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Abstract
When the virus dose is increased from 102 (low dose) to 104 LD50 (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 TD 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 (Ts) 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 TD response is sensitive to larger amounts of virus antigen. We conclude that this impairment and the resulting DTH unresponsiveness is due to a clonal deletion or energy rather than to the effect of Ts cells, and that the TD effector function is critical to the development of fatal LCM disease.

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