Protection of adult but not newborn mice against lethal intracerebral challenge with Japanese encephalitis virus by adoptively transferred virus-specific cytotoxic T lymphocytes: requirement for L3T4⁺ T cells

Abstract

The protective ability of cytotoxic T cells (CTL) raised in vitro against Japanese encephalitis virus (JEV) was examined by adoptive transfer experiments. Adoptive transfer of anti-JEV effectors by intracerebral (i.c.) but not by intraperitoneal (i.p.) or intravenous (i.v.) routes protected adult BALB/c mice against lethal i.c. JEV challenge. In contrast to adult mice, adoptive transfer of anti-JEV effectors into newborn (4-day-old) and suckling (8-14-day-old) mice did not confer protection. However, virus-induced death was delayed in suckling mice compared to newborn mice upon adoptive transfer. The specific reasons for lack of protection in newborn mice are not clear but virus load was found to be higher in newborn mice brains compared to those of adults and virus clearance was observed only in adult mice brains but not in newborn mice brains upon adoptive transfer. Specific depletion of Lyt 2.2⁺, L3T4⁺ or Thy-1⁺ T cell populations before adoptive transfer abrogated the protective ability of transferred effectors. However, when Lyt 2.2⁺ cell-depleted and L3T4⁺ cell-depleted effectors were mixed and transferred into adult mice the protective activity was retained, demonstrating that both Lyt 2.2⁺ and L3T4⁺ T cells are necessary to confer protection. Although the presence of L3T4⁺ T cells in adoptively transferred effector populations enhanced virus-specific serum neutralizing antibodies, the presence of neutralizing antibodies alone without Lyt 2.2⁺ cells was not sufficient to confer protection.