PARTICIPATION OF CYCLOPHOSPHAMIDE-RESISTANT T-CELLS IN MURINE LYMPHOCYTIC CHORIOMENINGITIS

A severe inflammatory process can be induced by transferring lymphocytic choriomeningitis virus (LCMV)-immune spleen cell populations into cyclophosphamide (Cy)-suppressed, LCMV-infected recipients. The extent of cellular invasion can be quantified accurately by counting cells obtained from the cisterna magna. The underlying lymphocyte-target cell interactions are apparently very specific, with massive cellular invasion being dependent on the donor and recipient sharing class I major histocompatibility complex glycoproteins. Unlike the situation found by others for delayed-type hypersensitivity in the mouse footpad, the inflammatory process in the cisterna magna was induced to a similar extent by unmanipulated LCMV-immune spleen cells and by lymphocyte populations from mice that were pretreated with 150-200 mg/kg of Cy. This dose of Cy did not eliminate cytotoxic T lymphocytes (CTL) in the mouse strains used. Immune spleen cells from Cy-pretreated mice showed a reduced capacity to clear virus from the brain. Virus persisted even though the inflammatory process resolved. Evidently, immune CTL are directly responsible for the induction of severe meningitis in LCM, although CTL obviously do not constitute the sole effectors involved in eliminating virus from the CNS.