| First Author | Butler NS | Year | 2011 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 2 | Pages | 188-95 |
| PubMed ID | 22157630 | Mgi Jnum | J:180796 |
| Mgi Id | MGI:5307220 | Doi | 10.1038/ni.2180 |
| Citation | Butler NS, et al. (2012) Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection. Nat Immunol 13(2):188-95 |
| abstractText | Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite persistence remain unknown. Here we show that infection of humans with Plasmodium falciparum resulted in higher expression of the inhibitory receptor PD-1 associated with T cell dysfunction. In vivo blockade of the PD-1 ligand PD-L1 and the inhibitory receptor LAG-3 restored CD4(+) T cell function, amplified the number of follicular helper T cells and germinal-center B cells and plasmablasts, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, and proper function can be restored by inhibitory therapies to enhance parasite control. |
