Mice lacking Programmed cell death-1 show a role for CD8(+) T cells in long-term immunity against blood-stage malaria

• Published in: Scientific reports Vol. 6; no. 1; p. 26210
• Main Authors: Horne-Debets, Joshua M, Karunarathne, Deshapriya S, Faleiro, Rebecca J, Poh, Chek Meng, Renia, Laurent, Wykes, Michelle N
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 24.05.2016
• Subjects: Animals; Apoptosis; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell death; Clonal deletion; Disease Models, Animal; Immune response; Infections; Lymphocytes; Lymphocytes B; Lymphocytes T; Malaria; Malaria - immunology; Mice, Inbred C57BL; Mice, Knockout; Parasitemia; PD-1 protein; Plasmodium chabaudi - immunology; Programmed Cell Death 1 Receptor - deficiency; Programmed Cell Death 1 Receptor - metabolism; Rodents
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep26210

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.