Abstract:
: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.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Butler NS,Moebius J,Pewe LL,Traore B,Doumbo OK,Tygrett LT,Waldschmidt TJ,Crompton PD,Harty JTdoi
10.1038/ni.2180subject
Has Abstractpub_date
2011-12-11 00:00:00pages
188-95issue
2eissn
1529-2908issn
1529-2916pii
ni.2180journal_volume
13pub_type
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