title: Mice lacking Programmed cell death-1 show a role for CD8(+) T cells in long-term immunity against blood-stage malaria.
abstract: Even after years of experiencing malaria, caused by infection with Plasmodium species, individuals still have incomplete immunity and develop low-density parasitemia on re-infection. Previous studies using the P. chabaudi (Pch) mouse model to understand the reason for chronic malaria, found that mice with a deletion of programmed cell death-1 (PD-1KO) generate sterile immunity unlike wild type (WT) mice. Here we investigated if the mechanism underlying this defect during acute immunity also impacts on long-term immunity. We infected WT and PD-1KO mice with Pch-malaria and measured protection as well as immune responses against re-infections, 15 or 20 weeks after the original infection had cleared. WT mice showed approximately 1% parasitemia compared to sterile immunity in PD-1KO mice on re-infection. An examination of the mechanisms of immunity behind this long-term protection in PD-1KO mice showed a key role for parasite-specific CD8(+) T cells even when CD4(+) T cells and B cells responded to re-infection. These studies indicate that long-term CD8(+) T cell-meditated protection requires consideration for future malaria vaccine design, as part of a multi-cell type response.
authors.affiliation: The QIMR Berghofer Medical Research Institute, Infectious Disease Programme, Queensland, 4029, Australia.|The School of Medicine, University of Queensland, Brisbane 4072, Australia.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Horne-Debets
authors.affiliation: The QIMR Berghofer Medical Research Institute, Infectious Disease Programme, Queensland, 4029, Australia.
authors.forename: Deshapriya S
authors.initials: DS
authors.lastname: Karunarathne
authors.affiliation: The QIMR Berghofer Medical Research Institute, Infectious Disease Programme, Queensland, 4029, Australia.|The School of Medicine, University of Queensland, Brisbane 4072, Australia.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Faleiro
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 136648, Singapore.|Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
authors.forename: Chek Meng
authors.initials: CM
authors.lastname: Poh
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 136648, Singapore.|Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
authors.forename: Laurent
authors.initials: L
authors.lastname: Renia
authors.affiliation: The QIMR Berghofer Medical Research Institute, Infectious Disease Programme, Queensland, 4029, Australia.
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Wykes
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D008288:Malaria / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016788:Plasmodium chabaudi / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000172:deficiency / Q000378:metabolism*
chemical_list: C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor