Limiting the available T cell receptor repertoire modifies acute lymphocytic choriomeningitis virus-induced immunopathology.
The invariably fatal immunopathological disease that follows intracerebral injection of CBA/Ca (H-2k) mice with 1000 PFU of lymphocytic choriomeningitis virus (LCMV) generally fails to develop in congenic mice transgenic for a V beta 8.1D beta 2J beta 2.3C beta 2 T cell receptor (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 depends on the involvement of V beta 8+ T cells, but does not require the participation of the CD4+ subset. The cytotoxic effectors that develop in both the transgenic mice and the CBA/Ca controls are lytic for target cells infected with a vaccinia construct expressing genes encoding the putative polymerase protein of LCMV. Limiting the available TCR repertoire to lymphocytes with a single V beta phenotype (not required for the generation of potent effectors in wild-type mice) thus modifies the development of the lethal neuropathology characteristic of LCMV infection, although the CD8+ cytotoxic T lymphocyte response is not greatly compromised.
Doherty
P C
PC
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105.
Hou
S
S
Evans
C F
CF
Whitton
J L
JL
Oldstone
M B
MB
Blackman
M A
MA
D000208:Acute Disease; D000818:Animals; D005260:Female; D008216:Lymphocytic Choriomeningitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta