Display Settings:

Format

Send to:

Choose Destination
Nat Immunol. 2009 Jan;10(1):29-37. doi: 10.1038/ni.1679. Epub 2008 Nov 30.

Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.

Author information

  • 1Immunology Program and Wistar Vaccine Center, Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

Abstract

T cell exhaustion often occurs during chronic infection and prevents optimal viral control. The molecular pathways involved in T cell exhaustion remain poorly understood. Here we show that exhausted CD8+ T cells are subject to complex layers of negative regulation resulting from the coexpression of multiple inhibitory receptors. Exhausted CD8+ T cells expressed up to seven inhibitory receptors. Coexpression of multiple distinct inhibitory receptors was associated with greater T cell exhaustion and more severe infection. Regulation of T cell exhaustion by various inhibitory pathways was nonredundant, as blockade of the T cell inhibitory receptors PD-1 and LAG-3 simultaneously and synergistically improved T cell responses and diminished viral load in vivo. Thus, CD8+ T cell responses during chronic viral infections are regulated by complex patterns of coexpressed inhibitory receptors.

PMID:
19043418
[PubMed - indexed for MEDLINE]
PMCID:
PMC2605166
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk