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Human T Lymphocyte Isolation, Culture and Analysis of Migration In Vitro
Published on: June 1, 2010
Lymphocyte migration into brain modelled in vitro: control by lymphocyte activation, cytokines, and antigen
1Department of Neuropathology, Institute of Psychiatry, Denmark Hill, London, United Kingdom.
Insights
Lymphocyte adhesion to brain endothelium increases with activation and requires protein synthesis. Cytokine stimulation of endothelium also enhances this adhesion, impacting immune cell traffic into the brain.
Area of Science:
- Neuroimmunology
- Cellular Immunology
Background:
- Lymphocyte adhesion to brain endothelium is crucial for immune surveillance and response within the central nervous system.
- Understanding the factors that regulate this adhesion is key to modulating immune cell infiltration into the brain.
Purpose of the Study:
- To investigate the in vitro factors controlling lymphocyte adhesion to rat brain endothelium.
- To determine the roles of lymphocyte activation and endothelial stimulation in modulating adhesion.
Main Methods:
- In vitro assays measuring lymphocyte-endothelium adhesion.
- Stimulation of lymphocytes with mitogens and endothelium with interferon-gamma (IFN-γ).
- Assessment of adhesion in the presence of cognate antigen.
Main Results:
- Mitogen-activated lymphocytes showed increased adhesion to endothelium, peaking at 7-24 hours and requiring protein synthesis.
- Interferon-gamma (IFN-γ) stimulation of rat brain endothelium increased adhesion of both normal and activated lymphocytes.
- Antigen-specific lymphocytes adhered more effectively, with further enhancement by IFN-γ and cognate antigen.
Conclusions:
- Both lymphocyte activation and endothelial stimulation with cytokines significantly modulate lymphocyte adhesion to brain endothelium.
- These findings suggest mechanisms for controlling immune cell traffic into the brain via peripheral lymphocyte activation or local endothelial cytokine signaling.
Abstract:
Factors controlling lymphocyte adhesion to brain endothelium were investigated in vitro. Mitogen activation of lymphocytes causes increased adhesion to endothelium, which is maximal at 7-24 hr, declines to normal levels after the cells divide, and requires protein synthesis. Rat brain endothelium can be stimulated with IFN-gamma to increase its adhesion to either normal or activated lymphocytes. The endothelium is sensitive to low levels of cytokine: adhesion develops rapidly after stimulation and requires new protein synthesis. Antigen-specific line cells also adhere more effectively to endothelium than normal lymph node cells. This is enhanced by IFN-gamma treatment of the endothelium and is further increased marginally in the presence of the cognate antigen. The results suggest that either local stimulation of endothelium with cytokines or lymphocyte activation in the periphery will modulate lymphocyte traffic into brain.
