IFN-induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections.
J Immunol
; 176(7): 4284-95, 2006 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-16547266
ABSTRACT
Profound lymphopenia has been observed during many acute viral infections, and our laboratory has previously documented a type I IFN-dependent loss of CD8 T cells immediately preceding the development of the antiviral T cell response. Most memory (CD44(high)) and some naive (CD44(low)) CD8 T cells are susceptible to IFN-induced attrition, and we show in this study that the IFN-induced attrition of CD8(+)CD44(high) T cells is associated with elevated activation of caspase-3 and caspase-8. We questioned whether TCR engagement by Ag would render CD8 T cells resistant to attrition. We tested whether a high concentration of Ag (GP33 peptide) would protect lymphocytic choriomeningitis (LCMV)-specific naive CD8 T cells (TCR transgenic P14 cells specific for the GP33 epitope of LCMV) and memory CD8 T cells (GP33-specific LCMV-immune cells) from depletion. Both naive P14 and memory GP33-specific donor CD8 T cells decreased substantially 16 h after inoculation with the Toll receptor agonist and IFN inducer, poly(IC), regardless of whether a high concentration of GP33 peptide was administered to host mice beforehand. Moreover, donor naive P14 and LCMV-specific memory cells were depleted from day 2 LCMV-infected hosts by 16 h posttransfer. These results indicate that Ag engagement does not protect CD8 T cells from the IFN-induced T cell attrition associated with viral infections. In addition, computer models indicated that early depletion of memory T cells may allow for the generation for a more diverse T cell response to infection by reducing the immunodomination caused by cross-reactive T cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Proteínas Virais
/
Glicoproteínas
/
Interferons
/
Linfócitos T CD8-Positivos
/
Coriomeningite Linfocítica
/
Vírus da Coriomeningite Linfocítica
/
Antígenos Virais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2006
Tipo de documento:
Article