LIMITING THE AVAILABLE T-CELL RECEPTOR REPERTOIRE MODIFIES ACUTE LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INDUCED IMMUNOPATHOLOGY

The invariably fatal immunopathological disease that follows intracere bral injection of CBA/Ca (H-2(k)) mice with 1000 PFU of lymphocytic ch oriomeningitis virus (LCMV) generally fails to develop in congenic mic e transgenic for a V beta 8.1D beta 2J beta 2.3C beta 2 T cell recepto r (TCR) gene. The majority of these LCMV-infected TCR-transgenic mice show a substantial meningitis of delayed onset, that resolves without causing any obvious clinical impairment. This inflammatory process dep ends on the involvement of V beta 8(+) T cells, but does not require t he participation of the CD4(+) subset. The cytotoxic effecters that de velop in both the transgenic mice and the CBA/Ca controls are lytic fo r target cells infected with a vaccinia construct expressing genes enc oding the putative polymerase protein of LCMV. Limiting the available TCR repertoire to lymphocytes with a single V beta phenotype (not requ ired for the generation of potent effecters in wild-type mice) thus mo difies the development of the lethal neuropathology characteristic of LCMV infection, although the CD8(+) cytotoxic T lymphocyte response is not greatly compromised.