Trial reportThe Journal of clinical investigation2020
CD8+ T cells target cerebrovasculature in children with cerebral malaria.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed.
- The Impact of Antigen Presentation on BBB Disruption and Neuroinflammation.Physiology (Bethesda, Md.) · 2026Review
- Bradykinin contributes to vasogenic edema in murine experimental cerebral malaria.The Journal of clinical investigation · 2026Article
- ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis.EMBO molecular medicine · 2026Article
- Safety, Tolerability, and Pharmacokinetics of 6-Diazo-5-Oxo-L-Norleucine in Malawian Adults With and Without Malaria: A Phase 1 Dose-Escalation Clinical Trial.The Journal of infectious diseases · 2026Article
- Methylene blue treatment of fatal cerebral malaria and identification of potential blood biomarkers.Nature communications · 2025Article
- Plasmodium falciparum impairs Ang-1 secretion by pericytes in a 3D brain microvessel model.EMBO molecular medicine · 2025Article
- Neurovascular Pathophysiology and Emerging Biomarkers in Cerebral Malaria: An Integrative Perspective.Neurology international · 2025Review
- Potential of microRNAs as diagnostic markers for distinguishing malaria severity in samples from an Indian cohort.BMC infectious diseases · 2025Article
- Article
- Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model.Nature communications · 2025Article
- NR2F6 as a Disease Driver and Candidate Therapeutic Target in Experimental Cerebral Malaria.Cells · 2025Article
- Plasmodium falciparum infection induces T cell tolerance that is associated with decreased disease severity upon re-infection.The Journal of experimental medicine · 2025Article
- Resolution of experimental malaria-associated acute respiratory distress syndrome is Alox12 independent and shows residual inflammation.Malaria journal · 2025Article
- CD8 T cells as drivers of blood-brain barrier disruption.Trends in neurosciences · 2025Review
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- CXCL10CNS neuroscience & therapeutics · 2025Article
- Leveraging microphysiological systems to expedite understanding of host-parasite interactions.PLoS pathogens · 2025Review
- Microbiome-mediated modulation of immune memory to P. yoelii affects the resistance to secondary cerebral malaria challenge.ImmunoHorizons · 2025Article
- Optimizing Colocalized Cell Counting Using Automated and Semiautomated Methods.Neuroinformatics · 2025Article
- Severe malaria enforces short-lived effector cell differentiation but does not prevent effective secondary responses by memory CD8 T cells.PLoS pathogens · 2025Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors.
Funding
Abstract
BACKGROUNDCerebral malaria (CM) accounts for nearly 400,000 deaths annually in African children. Current dogma suggests that CM results from infected RBC (iRBC) sequestration in the brain microvasculature and resulting sequelae. Therapies targeting these events have been unsuccessful; findings in experimental models suggest that CD8+ T cells drive disease pathogenesis. However, these data have largely been ignored because corroborating evidence in humans is lacking. This work fills a critical gap in our understanding of CM pathogenesis that is impeding development of therapeutics.METHODSUsing multiplex immunohistochemistry, we characterized cerebrovascular immune cells in brain sections from 34 children who died from CM or other causes. Children were grouped by clinical diagnosis (CM+ or CM-), iRBC sequestration (Seqhi, Seqlo, Seq0) and HIV status (HIV+ or HIV-).RESULTSWe identified effector CD3+CD8+ T cells engaged on the cerebrovasculature in 69% of CM+ HIV- children. The number of intravascular CD3+CD8+ T cells was influenced by CM status (CM+ > CM-, P = 0.004) and sequestration level (Seqhi > Seqlo, P = 0.010). HIV coinfection significantly increased T cell numbers (P = 0.017) and shifted cells from an intravascular (P = 0.004) to perivascular (P < 0.0001) distribution.CONCLUSIONWithin the studied cohort, CM is associated with cerebrovascular engagement of CD3+CD8+ T cells, which is exacerbated by HIV coinfection. Thus, CD3+CD8+ T cells are highly promising targets for CM adjunctive therapy, opening new avenues for the treatment of this deadly disease.FUNDINGThis research was supported by the Intramural Research Program of the National Institutes of Health.
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