MENU ▼
Read by QxMD icon Read
search
OPEN IN READ APP
JOURNAL ARTICLE

Restoring function in exhausted CD8 T cells during chronic viral infection

Daniel L Barber, E John Wherry, David Masopust, Baogong Zhu, James P Allison, Arlene H Sharpe, Gordon J Freeman, Rafi Ahmed
Nature 2006 February 9, 439 (7077): 682-7
16382236
Functional impairment of antigen-specific T cells is a defining characteristic of many chronic infections, but the underlying mechanisms of T-cell dysfunction are not well understood. To address this question, we analysed genes expressed in functionally impaired virus-specific CD8 T cells present in mice chronically infected with lymphocytic choriomeningitis virus (LCMV), and compared these with the gene profile of functional memory CD8 T cells. Here we report that PD-1 (programmed death 1; also known as Pdcd1) was selectively upregulated by the exhausted T cells, and that in vivo administration of antibodies that blocked the interaction of this inhibitory receptor with its ligand, PD-L1 (also known as B7-H1), enhanced T-cell responses. Notably, we found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the 'helpless' CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load. Blockade of the CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) inhibitory pathway had no effect on either T-cell function or viral control. These studies identify a specific mechanism of T-cell exhaustion and define a potentially effective immunological strategy for the treatment of chronic viral infections.

Comments

You need to log in or sign up for an account to be able to comment.

M Villanueva wrote:

0

New evidence about T cell exhaustion and infectious diseases. Reinforce the recent paper published NEJM Pembrolizumab and JC virus

keke pomers wrote:

0

Great

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
16382236
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"