ArticleFluids and barriers of the CNS2020
Human CD4
Article in Fluids and barriers of the CNS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Shared Genetic Risk Factors for Multiple Sclerosis/Psoriasis Suggest Involvement of Interleukin-17 and Janus Kinase-Signal Transducers and Activators of Transcription Signaling.Annals of neurology · 2023Pooled it
- Non-canonical cleavage of GPR125/ADGRA3 releases extracellular receptor fragments detectable in cerebrospinal fluid.iScience · 2026Article
- Establishment and Optimization of a Human Flow-Based Hollow FiberPharmaceutics · 2026Article
- Targeting CD4⁺ T cell infiltration: mechanisms and therapeutic insights into CD4⁺ T cell transmigration across the blood-brain barrier in acute ischemic stroke.Fluids and barriers of the CNS · 2026Review
- The microenvironment of glioblastoma: in pursuit of universal multimodal immunotherapy.Acta neurologica Belgica · 2026Review
- The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Immunological Insights into Photodynamic Therapy of Glioblastoma Multiforme.Molecules (Basel, Switzerland) · 2025Review
- Article
- CD4+ T cell-innate immune crosstalk is critical during Staphylococcus aureus craniotomy infection.JCI insight · 2025Article
- Choroid plexus organoids reveal mechanisms of Streptococcus suis translocation at the blood-cerebrospinal fluid barrier.Fluids and barriers of the CNS · 2025Article
- Interaction between Th17 and central nervous system in multiple sclerosis.Brain, behavior, & immunity - health · 2025Review
- Transcriptional Responses of In Vitro Blood-Brain Barrier Models to Shear Stress.Biomolecules · 2025Article
- The critical role of Th17 cells and IL-17A in autoimmune and inflammation-associated neurological diseases: mechanisms and therapeutic perspectives.Frontiers in immunology · 2025Review
- Tension at the gate: sensing mechanical forces at the blood-brain barrier in health and disease.Journal of neuroinflammation · 2024Review
- Engineering memory T cells as a platform for long-term enzyme replacement therapy in lysosomal storage disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Review
- T Cells Trafficking into the Brain in Aging and Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Review
- CD4Neurobiology of stress · 2024Article
- Sex- and species-specific contribution of CD99 to T cell costimulation during multiple sclerosis.Biology of sex differences · 2024Article
- Brain regulatory T cells.Nature reviews. Immunology · 2024Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 8 institutions in 7 countries.
Funding
Abstract
backgroundThe brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood-brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP).
objectiveAnalysis of the cellular and molecular mechanisms involved in the migration of different human CD4
methodsHuman in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4
resultsWhile under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration.
conclusionsOur observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.