IMMUNOLOGY2024™ Conference Recordings-Defining the characteristics of pathogenic CD8+ T cells in malaria

Video Transcription

Video Summary

The speaker discussed malaria pathogenesis, focusing on severe disease and cerebral malaria. They explained that while many Plasmodium infections are asymptomatic or mild, some progress to life-threatening complications, especially when parasites sequester in organs like the brain. In both humans and a mouse model of experimental cerebral malaria, the blood-brain barrier becomes disrupted, leading to brain swelling and death.<br /><br />A major theme was the role of CD8 T cells. Evidence from human samples and mouse depletion studies showed these cells infiltrate the brain, recognize parasite antigens presented by endothelial cells, and contribute to blood-brain barrier breakdown through interferon gamma, granzyme B, and inflammatory signaling.<br /><br />The lab focused on the GAP50 malaria epitope and found, using sensitive binding assays, that most parasite-specific CD8 T cells are surprisingly low affinity. These low-affinity cells are still functional and pathogenic. In contrast, high-affinity cells appeared less inflammatory and may even be more regulatory, expressing molecules such as IL-10 and arginase 1.<br /><br />They also found the same low-affinity bias in liver-stage CD8 T-cell responses after sporozoite infection, suggesting this may be a broader malaria feature. The talk ended by emphasizing the need to understand T-cell affinity and function to improve malaria vaccine strategies.

Keywords

malaria

cerebral malaria

CD8 T cells

blood-brain barrier

parasite sequestration

T-cell affinity

vaccine strategy