VIRUS-SPECIFIC CD8-CELL RESPONSES IN MICE TRANSGENIC FOR A T-CELL RECEPTOR BETA-CHAIN SELECTED AT RANDOM( T)

Citation
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
Citations number
29
Categorie Soggetti
Virology
Journal title
ISSN journal
0022538X
Volume
68
Issue
5
Year of publication
1994
Pages
3065 - 3070
Database
ISI
SICI code
0022-538X(1994)68:5<3065:VCRIMT>2.0.ZU;2-1
Abstract
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.