| First Author | Blackburn SD | Year | 2009 |
| Journal | Nat Immunol | Volume | 10 |
| Issue | 1 | Pages | 29-37 |
| PubMed ID | 19043418 | Mgi Jnum | J:142341 |
| Mgi Id | MGI:3821397 | Doi | 10.1038/ni.1679 |
| Citation | Blackburn SD, et al. (2009) Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 10(1):29-37 |
| abstractText | 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. |
