C. Ewing et al., VIRUS-SPECIFIC CD8-CELL RESPONSES IN MICE TRANSGENIC FOR A T-CELL RECEPTOR BETA-CHAIN SELECTED AT RANDOM( T), Journal of virology, 68(5), 1994, pp. 3065-3070
The consequences of severely limiting the T-cell receptor (TCR) repert
oire available for the response to intranasal infection with an influe
nza A virus or with Sendai virus have been analyzed by using H-2(k) mi
ce (TG8.1) transgenic for a TCR beta-chain gene (V beta 8.1D beta 2J b
eta 2.3C beta 2). Analyzing tire prevalence of V beta 8.1(+) CD8(+) T
cells in lymph node cultures from nontransgenic (non-TG) H-2(k) contro
ls primed with either virus and then stimulated in vitro with the homo
logous virus or with anti-CD3 epsilon shelved that this TCR is not nor
mally selected from the CD8(+) T-cell repertoire during these infectio
ns. However, the TG8.1 mice cleared both viruses and generated virus-S
pecific effector cytotoxic T lymphocytes (CTL) and memory CTL precurso
rs, though the: responses were delayed compared with the non-TG contro
ls. Depletion of the CD4(+) T-cell subset had little effect on the cou
rse of influenza virus infection but substantially slowed the developm
ent of the Sendai virus-specific CTL response and virus elimination in
both the TG8.1 and non-TG mice, indicating that CD4(+) helpers are pr
omoting the CD8(+) T-cell response in the Sendai virus model. Even so,
restricting the available T-cell repertoire to lymphocytes expressing
a single TCR beta chain stilt allows sufficient TCR diversity for CD8
(+) T cells (acting in the presence or absence of the CD4(+) subset) t
o limit infection with an influenza A virus and a parainflueuza type 1
virus.