| First Author | Kurup SP | Year | 2017 |
| Journal | Nat Med | Volume | 23 |
| Issue | 10 | Pages | 1220-1225 |
| PubMed ID | 28892065 | Mgi Jnum | J:251213 |
| Mgi Id | MGI:6103705 | Doi | 10.1038/nm.4395 |
| Citation | Kurup SP, et al. (2017) Regulatory T cells impede acute and long-term immunity to blood-stage malaria through CTLA-4. Nat Med 23(10):1220-1225 |
| abstractText | Malaria, caused by the protozoan Plasmodium, is a devastating mosquito-borne disease with the potential to affect nearly half the world''s population. Despite mounting substantial T and B cell responses, humans fail to efficiently control blood-stage malaria or develop sterilizing immunity to reinfections. Although forkhead box P3 (FOXP3)(+)CD4(+) regulatory T (Treg) cells form a part of these responses, their influence remains disputed and their mode of action is unknown. Here we show that Treg cells expand in both humans and mice in blood-stage malaria and interfere with conventional T helper cell responses and follicular T helper (TFH)-B cell interactions in germinal centers. Mechanistically, Treg cells function in a critical temporal window to impede protective immunity through cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). Targeting Treg cells or CTLA-4 in this precise window accelerated parasite clearance and generated species-transcending immunity to blood-stage malaria in mice. Our study uncovers a critical mechanism of immunosuppression associated with blood-stage malaria that delays parasite clearance and prevents development of potent adaptive immunity to reinfection. These data also reveal a temporally discrete and potentially therapeutically amenable functional role for Treg cells and CTLA-4 in limiting antimalarial immunity. |
