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Related Experiment Videos

Lymphocyte migration into the CNS modelled in vitro.

D Male1, G Pryce, A Linke

  • 1Department of Neuropathology, Institute of Psychiatry, London, UK.

Journal of Neuroimmunology
|October 1, 1992
PubMed
Summary

Lymphocyte migration across brain endothelium involves distinct adhesion and migration steps. Activated CD4+ T cells effectively cross, while other lymphocytes adhere but do not migrate, highlighting lymphocyte activation as a key factor.

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Area of Science:

  • Neuroimmunology
  • Cellular Biology
  • Endothelial Biology

Background:

  • Understanding lymphocyte trafficking to the central nervous system is crucial for neuroinflammatory diseases.
  • In vitro models are essential for dissecting the complex interactions between lymphocytes and brain endothelial cells.

Purpose of the Study:

  • To investigate the factors governing lymphocyte adhesion to and migration across brain endothelium.
  • To differentiate the processes of adhesion and transmigration.
  • To identify key molecular players and cell types involved in this interaction.

Main Methods:

  • Development and utilization of a novel in vitro migration assay.
  • Analysis of lymphocyte adhesion and transmigration using various lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells).

Related Experiment Videos

  • Investigation of the role of lymphocyte activation state and endothelial activation (cytokine treatment).
  • Antibody blocking studies targeting adhesion molecules like LFA-1/ICAM-1 and VLA-4/VCAM.

    • Main Results:

    • Lymphocyte adhesion precedes migration, but they are distinct processes.
    • Activated CD4+ T cells demonstrated significant migration capacity across brain endothelium.
    • CD8+ T cells and B cells adhered strongly but did not migrate.
    • Endothelium supported sustained cell traffic without disruption.
    • Lymphocyte activation state was the primary factor for migration, irrespective of endothelial activation.
    • Adhesion molecule kinetics suggested roles for LFA-1/ICAM-1 and VLA-4/VCAM.
    • Antibody blocking indicated LFA-1/ICAM-1 involvement, though ICAM-1 levels were not critical.

    Conclusions:

    • Lymphocyte activation state is a critical determinant for crossing the brain endothelial barrier.
    • Distinct adhesion molecule interactions, potentially involving LFA-1, mediate lymphocyte transmigration.
    • The brain endothelium maintains its integrity during lymphocyte trafficking.