| First Author | Dookie RS | Year | 2020 |
| Journal | Parasite Immunol | Volume | 42 |
| Issue | 9 | Pages | e12723 |
| PubMed ID | 32306409 | Mgi Jnum | J:298559 |
| Mgi Id | MGI:6480252 | Doi | 10.1111/pim.12723 |
| Citation | Dookie RS, et al. (2020) Combinatorial Tim-3 and PD-1 activity sustains antigen-specific Th1 cell numbers during blood-stage malaria. Parasite Immunol 42(9):e12723 |
| abstractText | AIMS: Co-inhibitory receptors play a major role in controlling the Th1 response during blood-stage malaria. Whilst PD-1 is viewed as the dominant co-inhibitory receptor restricting T cell responses, the roles of other such receptors in coordinating Th1 cell activity during malaria are poorly understood. METHODS AND RESULTS: Here, we show that the co-inhibitory receptor Tim-3 is expressed on splenic antigen-specific T-bet(+) (Th1) OT-II cells transiently during the early stage of infection with transgenic Plasmodium yoelii NL parasites expressing ovalbumin (P yoelii NL-OVA). We reveal that co-blockade of Tim-3 and PD-L1 during the acute phase of P yoelii NL infection did not improve the Th1 cell response but instead led to a specific reduction in the numbers of splenic Th1 OT-II cells. Combined blockade of Tim-3 and PD-L1 did elevate anti-parasite IgG antibody responses. Nevertheless, co-blockade of Tim-3 and PD-L1 did not affect IFN-gamma production by OT-II cells and did not influence parasite control during P yoelii NL-OVA infection. CONCLUSION: Thus, our results show that Tim-3 plays an unexpected combinatorial role with PD-1 in promoting and/ or sustaining a Th1 cell response during the early phase of blood-stage P. yoelii NL infection but combined blockade does not dramatically influence anti-parasite immunity. |
