On the role of the inhibitory receptor LAG-3 in acute and chronic LCMV infection.
Int Immunol
; 22(1): 13-23, 2010 Jan.
Article
em En
| MEDLINE
| ID: mdl-19880580
ABSTRACT
Chronic viral infections are often characterized by CD8 T-cell responses with poor cytokine secretion potential and limited expansion of the CD8 T-cell pool, collectively referred to as CD8 T-cell exhaustion. Exhaustion of lymphocytic choriomeningitis virus (LCMV)-specific CD8 T cells was shown to be partially regulated by the inhibitory receptor programmed death 1 (PD-1). Here, we demonstrate that exhausted LCMV-specific CD8 T cells also express the negative regulatory receptor lymphocyte activation gene 3 (LAG-3) which is mainly expressed on cells co-expressing the negative regulatory receptors PD-1 and Tim-3. Expression levels of LAG-3 on anti-viral CD8 T cells remain stable over short-term in vitro stimulations in presence of antigenic peptide. Nevertheless, in vitro and in vivo blockade of LAG-3 did not rescue cytokine production by virus-specific CD8 T cells and did not alter the virus titer in various organs. Likewise, chronic LCMV infection of LAG-3-/- mice led to a comparable degree of T-cell exhaustion as observed in C57BL/6 controls and to similar virus titers. Further, LAG-3 did not influence T-cell activation or cell division during chronic LCMV infection. These data suggest that even though LAG-3 is continuously up-regulated on LCMV-specific exhausted CD8 T cells, it alone does not significantly contribute to T-cell exhaustion.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antígenos CD
/
Linfócitos T CD8-Positivos
/
Proteínas Reguladoras de Apoptose
/
Coriomeningite Linfocítica
/
Vírus da Coriomeningite Linfocítica
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article