Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection.

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 Immunol

journal_title

Nature immunology

authors

Butler NS,Moebius J,Pewe LL,Traore B,Doumbo OK,Tygrett LT,Waldschmidt TJ,Crompton PD,Harty JT

doi

10.1038/ni.2180

subject

Has Abstract

pub_date

2011-12-11 00:00:00

pages

188-95

issue

2

eissn

1529-2908

issn

1529-2916

pii

ni.2180

journal_volume

13

pub_type

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