Apoptosis of JHMV-specific CTL in the CNS in the absence of CD4⁺ T cells

The role of CD4⁺ T cells in altering the activity of cytotoxic T lymphocytes (CTL) during infection of the central nervous system (CNS) by the neuroptropic JHMV strain of mouse hepatitis virus was examined. Adoptive transfer of in vitro activated CTL into CD4-depleted and control recipients showed that CTL were not effective in reducing JHMV replication within the CNS. The distribution of CD4⁺ and CD8⁺ T cells within the CNS during JHMV infection showed that the CD4⁺ T cells remained in perivascular and subarachnoid spaces and few entered the parenchyma. By contrast approximately half of the CD8⁺ T cells entered the parenchyma. In CD4-depleted mice the trafficking of CD8⁺ T cells was not inhibited; however, the majority of the cells were found to be apoptotic. These data suggested that CD4⁺ T cells were not required for CTL induction but were required for the maintenance of CTL viability. The limited role of CD4⁺ T cells in CTL induction was confirmed by comparison of CTL activity from CD4-depleted and control mice.